Streamlined and pre-set neuromodulators

ABSTRACT

Limited-number-of-use neuromodulator apparatuses that may be comfortably worn on the skin of a user to non-invasively apply transdermal electrical stimulation (TES). The apparatuses described herein may be include a flexible/bendable substrate and an elastomeric cover (e.g., formed of an elastomeric fabric). These apparatuses may be simplified, to run autonomously. These apparatuses may also include improved power management features.

CROSS REFERENCE TO RELATED APPLICATIONS

This patent application claims priority to U.S. Provisional PatentApplication No. 62/662,057, titled “SINGLE-USE NEUROSTIMULATORS,” filedon Apr. 24, 2018, and U.S. Provisional Patent Application No.62/818,098, titled “SINGLE-USE NEUROSTIMULATORS,” filed on Mar. 13,2019. Each of these applications is herein incorporated by reference inits entirety.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference in their entirety to the sameextent as if each individual publication or patent application wasspecifically and individually indicated to be incorporated by reference.

FIELD

Described herein are non-invasive neuromodulation apparatuses, includingdevices and systems, and methods of their use.

BACKGROUND

Noninvasive neuromodulation can effect nerves and neuronal activity(including modulating cognitive states, perception, and motor output)and have many other therapeutic effects, without requiring an invasiveprocedure. Transdermal electric stimulation (hereinafter “TES”) usingskin (e.g., scalp) electrodes has been used to affect brain function andnervous system function in humans and includes transcranial alternatingcurrent stimulation (hereinafter “tACS”), transcranial direct currentstimulation (hereinafter “tDCS”), cranial electrotherapy stimulation(hereinafter “CES”), transcranial random noise stimulation (hereinafter“tRNS”), trigeminal nerve stimulation (hereinafter “TNS”), and vagalnerve stimulation (“VNS”), amongst other forms known to those skilled inthe art.

TES has been used therapeutically in various clinical applications,including treatment of pain, depression, epilepsy, ADHD, and tinnitus.This neuromodulation has been demonstrated to lower physiological stressand anxiety, improve sleep, and has potential as a therapy for specificauto-immune disorders such as psoriasis. It has the potential to treatnumerous neurogenic inflammatory conditions. Neuromodulation has beenshown, for example, to result in increased energy and motivation. See,e.g., U.S. Pat. Nos. 9,014,811, 9,002,458, 9,233,244, 9,399,126 and9,333,334. The effect is comparable to caffeine or energy drinksavailable in the market today, though the effect can be stronger incertain individuals.

Despite the research to date on TES neuromodulation, existing systemsand methods for delivering TES are lacking. In particular, miniaturizedsystems that incorporate hardware components with a low profile,comfortable, and/or familiar form factor for convenient, intuitive, easyto use, comfortable, and on-the-go TES free from cumbersome electricalwires, have been lacking.

SUMMARY OF THE DISCLOSURE

Described herein are apparatuses, including devices (e.g.,neuromodulators) and systems (e.g., neuromodulation systems) that are orinclude a limited-use (1, 2, 3, 4, etc. uses), entirely self-containedwearable neuromodulator. These devices are specifically configured usingone or more of the features described herein to be lightweight (e.g., 20g or less, such as 19 g or less, 18 g or less, 17 g or less, 16 g orless, 15 g or less, 14 g or less, etc.) and highly flexible, whileresisting damage. The apparatuses may be thin (e.g., 1 cm thick or less,0.9 cm thick or less, 0.8 cm thick or less, 0.7 cm thick or less, 0.6 cmthick or less, 0.5 cm thick or less, 0.4 cm thick or less, 0.3 mc thickor less, etc.) including the power source, circuitry and electrode(s).Finally, these apparatuses may reliably and robustly deliver a therapywaveform (electrical waveform) that is effective to provide the one ormore neuromodulatory effects described explicitly herein, includinginducing an energized state, inducing a sympathetic nervous systemeffect, enhancing relaxation, enhancing a cognitive effect (e.g.,enhancing memory, etc.), and/or treating a disorder, includingneurogenic inflammatory conditions and autoimmune disorders such aspsoriasis.

In particular, these devices may be extremely simple and easy to use tolower the barrier of adoption. Any of these devices may be specificallyconfigured to operate robustly without requiring a user to adjust anycontrols. The apparatus may automatically turn on/off and may runautonomously. In some variations the apparatus may be configured to turnon (or be placed into a ‘ready’ mode) when released from its packagingor when a circuit interrupt is removed after removing from itspackaging. The circuit interrupt may be a pull tab, pin, deflectablecontact, or the like that may make an electrical connection between thepower supply (e.g., battery, capacitor, etc.) and the control circuitry.Upon removal from the skin, these devices may shut down automatically topreserve power and be ready for the next use without substantiallydraining the power source. Sensing and control circuits may eliminatefactors such as skin capacitance and soft tissue resistance to provide auniform amount of stimulation without regard to user-to-uservariability, thus eliminating the complex “intensity adjust dial” thatprior art stimulators used and thereby limited general adoption.

The neuromodulators (which may also be referred to equivalently hereinas neuromodulators) may be useful for either medical use and/or forconsumer applications; these apparatuses may be configured aslimited-number-of-use (e.g., single-use, useable for 2 sessions, useablefor 3 sessions, etc.), and may be disposable devices. The apparatusesdescried herein may have significant cost and use/compliance advantagesthat may enhance user's adoption and experience with the apparatus. Theneuromodulators described herein may be skin-wearable neuromodulationapparatuses that use very low power and are adapted for comfort. Thus,described herein are very low cost, limited-number-of-use/disposableproduct that are still capable of providing reliable and effectiveneuromodulation.

As mentioned above, the apparatuses described herein may be configuredto avoid controls and improve usage and compliance. In any of thevariations described herein, the apparatus may be configured so that itis adhesively secured to the skin via one or more regions of hydrogelmaterial. The hydrogel may be in contact with an electrode. In general,the apparatus may be configured as a thin, flexible ‘stack’ of laminatecomponents in which the electrodes (including the adhesive hydrogel) areon the substrate, while the power source and circuitry are positionedabove the substrate. In any of these apparatuses, the power source andcircuitry may be held between a flexible (e.g., fabric) cover thatencloses the power source and circuitry and in some variations wrapsaround them. A frame may hold the power source and/or circuitry and maybe attached to the substrate and/or it may be allowed to move (or‘float’) within the fabric enclosure relative to the substrate, whichmay enhance flexibility.

The apparatus may be any shape, e.g., round, oval, triangular,rectangular, etc. and may have rounded edges, and may be thin, e.g.,having thickness of less than about 1 cm (e.g., less than 0.8 cm, lessthan 0.7 cm, less than 0.5 cm, less than 0.4 cm, etc.) at the average ormaximum height. In some variations the maximum diameter of the apparatusmay be less than about 10 cm (e.g., less than about 9 cm, less thanabout 8 cm, less than about 7.5 cm, less than about 7 cm, less thanabout 6 cm, etc.). These dimensions, as well as the use of a fabricmaterial as the cover, may allow the device to be sufficientlylightweight (e.g., less than 20 g, less than 18 g, less than 17 g, lessthan 15 g, less than 12 g, etc.) so that the electrodes, andparticularly the hydrogel portion of the electrodes, may secure theapparatus to the subject's skin without requiring an additional supportor adhesive.

As mentioned, any of these devices may be configured so that theyinclude a circuit interrupt that prevents the power source from makingelectrical contact with the control circuitry until the circuitryinterrupt is manually or automatically removed. For example, theapparatus may be stored (packaged) ready for use but with the circuitinterrupt between the control circuit and the power source (e.g.,battery). When the circuit interrupt is removed, the battery may beplaced in electrical contact with the control circuit placing theapparatus into a ‘ready’ or standby mode, or in some variations maybegin applying the waveform.

Any of the apparatuses described herein may be configured so that theapparatus enters a standby/ready mode in which the waveform is notapplied until the apparatus confirms that the electrodes (e.g., thehydrogel) is in contact with skin, meaning it is safe to apply theenergy. Skin contact may be detected by, for example, detecting anelectrical property between the electrodes (e.g., anode and cathode)forming the apparatus. The electrical property may be (or may be relatedto or equivalent to) the impedance. The apparatus may periodically orcontinuously detect the electrical property (e.g., impedance) betweenthe electrodes and may permit the delivery of the waveform only when theelectrical property (e.g., impedance) is within a range of values thatindicate contact with skin.

In any of the apparatuses described herein, the device may not includeany other controls, and specifically may not have any controls foradjusting the applied waveform (including the intensity, frequency,duration, etc.). The waveform and it's time sequence of changes may bepredetermined and configured to achieve the desired effect as describedin greater detail below. The predetermined waveform may includeoperating for a predetermined time period (e.g., 4 minutes or more, 5minutes or more, 10 minutes or more, 12 minutes or more, 15 minutes ormore, 17 minutes or more, 20 minutes or more, etc.). Thus, the apparatusmay be extremely simple to operate.

The apparatuses described herein may be configured to allow two uses,three uses, or in some variations more than three uses (e.g., four uses,5 uses, etc.). Thus, the apparatus may be configured to be used once,then removed and used again later. For example, the apparatus may beconfigured to be removed from a packaging (e.g., a pouch, such as a foilpouch), and the circuit interrupt removed, peeled off of a liner so thatthe electrode(s) hydrogel is exposed and may be placed on the subject'sskin (e.g., neck, head, etc.) and allowed to deliver the waveform. Asmentioned above, the apparatus may detect that it's been placed on theskin and may operate autonomously to deliver the waveform until eitherthe waveform is completed (e.g., after the pre-determined duration) oruntil it is removed from the skin, which may be automatically detected.The device may then be in a delayed mode, and can be removed from theskin for re-applying later for a second use. In some variations thedevice may enter into a sleep or dormant mode until it can again delivera waveform. For example, the apparatus may enter into a dormant modethat lasts until it can be activated again (e.g., by detecting skincontact and/or automatically starting) after a predefined off-time,e.g., of 5 min or more, 10 min or more, 15 min or more, 20 min or more,30 min or more, etc. After the dormant mode, the device may bere-activated to deliver a subsequent (e.g., second) waveform, e.g.,after removal of a second circuit interrupt, such as a pull tab. Thesecond circuit interrupt may trigger the delivery of the subsequent usewaveform, which may be the same or different from the first usewaveform.

In variations including a second (or more) use configuration, theapparatus may include a second or additional hydrogel that is exposed byremoving all or part of the first set of electrode hydrogel. Forexample, a first outer layer of hydrogel may form part of a firstelectrode and a second outer layer of hydrogel may form part of a secondelectrode. Additional hydrogel layers may underlie the first and/orsecond hydrogel layers and may be separated by one or more releaselayers. After the outermost hydrogel layer(s) are used to deliver awaveform, the device may be removed from the skin and, beforere-applying the device to the skin, the user may remove the releaselayer to remove the outer layer(s) of hydrogel, exposing one or morenew, fresh hydrogel layers that are also in electrical contact with therest of the electrode. Alternatively or additionally, in some variationsthe hydrogel may be reactivated by adding a few drops of water. Any ofthe hydrogels may have a thickness sufficient to retain the device tothe uses but prevented from being too thick, which makes the devicetaller than desired and may reduce the electrical efficiency. Forexample, any of the hydrogel layers may have a thickness of the hydrogelof less than about 2 mm (e.g., less than about 1.75 mm, less than about1.5 mm, less than about 1.25 mm, less than about 1 mm, etc.).

In variations in which a release liner is included, the release linermay be connected to or may form part of the second circuit interrupt(e.g., pull tab) for activating or re-setting the control circuity sothat it enters into the second standby mode and prepares to deliver thesubsequent waveform when an electrical property detects the presence ofskin contact, as described above. Thus, in some variations, removing theouter hydrogel layer(s) (e.g., by removing the release layer and/orhydrogel) may remove the second circuit interrupt and allow activationof the second or subsequent waveform. The second or subsequentwaveform(s) may be different than first (or other predicate) waveform.For example the subsequent waveforms may be lower in one or more of:frequency and/or intensity. For example, the second waveform may have anamplitude that is between about 10-30% lower in amplitude compared tothe first waveform.

The release liner may be formed of a generally non-conductive material(e.g., electrically insulating material), but may have openings throughwhich the adjacent layers of hydrogel may be in contact.

In general the waveforms described herein may be configured so that theydeliver a constant current and a variable voltage; the voltage may bescaled between the first and subsequent waveforms. Examples andcharacteristics of effective predetermined waveforms are describedbelow; for example, a predefined waveform may have a frequency ofbetween about 100 Hz and 15 KHz and/or a charge per phase of between0.1-10 microCoulombs. In some variations the waveform may have a dutycycle of between 1% and 50%.

In general, the apparatuses and methods described herein may beconfigured to deliver a change per phase that is between about 0.1microCoulombs per phase and about 20 μC/phase (e.g., between about 0.1μC/phase and about 10 μC/phase, e.g. between about 0.2 μC/phase andabout 7 μC/phase, between about 0.2 μC/phase and about 5 μC/phase,between about 0.2 μC/phase and about 4μC/phase, etc.). In general, thefrequency may be configured to be between about 100 Hz and about 16 KHz,the percent duty cycle (e.g., the ratio of on to off time for thewaveform) may be between about 1% and about 50%, and the percent DC maybe between about 5% and 100%. In any of the apparatuses and methodsdescribed herein the waveform parameters may be specific to theindication for which the apparatus is intended. For example, theapparatuses described herein may include a pre-defined waveform that ismonophasic or biphasic; in some variations, such as the use of theapparatuses described herein to treat a dermatological or othertherapeutic indication, a biphasic waveform may be used, and the chargeper phase may be between about 0.1 μC/phase and 4 μC/phase; thefrequency may be between about 400 Hz and about 5 KHz (e.g., between 500Hz and 4 KHz). The percent duty cycle may be between about 10% and about40%, and the DC percentage may be between about 1%-70% (e.g., 4%-65%).The device may be applied to the back/midline of the user's neck.

In some variations, for indications in which an energizing effect isintended, the charge per phase may be between about 0.5 μC/phase andabout 2 μC/phase, and the frequency may be between about 100 Hz andabout 1600 Hz. The percent duty cycle may be between about 1% and about20%, and the DC percentage may be between about 90%-100%. The device maybe applied slightly behind the user's ear (e.g., over the mastoidregion).

Indications in which a relaxation effect is intended, the device may beapplied to the back of the user's neck (e.g., on or near the midline)and the charge per phase may be between about 0.1 and about 5 μC/phase.(e.g., between about 0.2 and about 3 μC/phase), and the frequency may bebetween about 1 KHz to about 16 KHz (e.g. between about 2 KHz and about15 KHz). The percent duty cycle may be between about 10% and about 50%,and the DC percentage may be between about 70%-100%.

In indications in which memory enhancements are intended, the device maybe applied to the forehead and/or temple regions with a common referenceelectrode targeting the prefrontal cortex and other brain regions, asinusoidal, theta-like wave with a frequency of between 4-8 Hz and abiphasic peak to peak intensity of 1.5 mA may be applied for a period ofat least 5 minutes.

The methods and apparatuses described herein may, in particular, beconfigured so that the waveforms shift (or oscillate) around one or moreof frequency, center amplitude or center duty cycle by between 2% and30% during the course of the application of the waveform. Theoscillation can be variable or constant. Such waveforms may be referredto as pendulum waveforms. For example, a pendulum waveform ‘swings’ backand forth around a center frequency, center amplitude, or center dutycycle. In some variations the frequency is oscillated about a centerfrequency and the oscillations do not have to be symmetric. The pendulumcycle may take, e.g., 2 to 20 seconds (e.g. about 7-9 seconds, such asabout 8 seconds) for the full cycle. The oscillation may be stepped(e.g., changed abruptly) or smooth (e.g., changed in a sinusoidalmanner).

Pendulum waveforms may provide an improvement because the change oroscillation in parameters are generally better since they preventadaptation. By sweeping over a range, the sensation and effect may bemore likely to work for a larger number of different people, who mayotherwise vary anatomically and biologically in that particular regionwith respect to nerve anatomy/physiology and sensory responses.

As mentioned above, any of the apparatuses described herein may includea fabric, and in particular an elastomeric fabric, material. The use ofan elastomeric fabric as part of the body of the device (including thecover, and/or in some variations the substrate) may enhance theflexibility, reduce the profile/size, and may reduce the weight of theapparatus. As used herein a fabric may include woven and non-wovenfabrics, including fabrics formed of sheets or layers of syntheticmaterial (e.g., plastics, polymers, etc.). In some variations the fabricmay be a highly compliant material. Examples of appropriate fabrics mayinclude, but are not limited to: elastomeric polymers, elastomericcotton (e.g., cotton/nylon blends, such as 95% cotton, 5% nylon, etc.),synthetic fibers, nylon fabrics, etc.

The fabric material may be used to wrap and/or cover the power sourceand/or control circuitry, and may be coupled to (e.g., adhesively bondedto) the substrate for the electrodes. In any of these variations thefabric may include an adhesive on one side, such as an acrylic adhesive.The fabric may form a cover that is compliant, and encloses all or partof the power supply and/or the circuitry. The fabric material may bewoven, knitted, braided, or the like.

Any of the apparatuses described herein may include one or more pairs ofelectrodes (anode/cathode), and/or may have a three-electrodeconfiguration (e.g., two cathodes, one anode). The electrodes mayinclude a hydrogel that is electrically conductive and configured tocontact the subject's skin. In general, the electrodes (including thehydrogel) may be arranged on a substrate so that they do not require aparticular orientation. For example, the electrode may be arrangedconcentrically, so that a first electrode at least partially (e.g., 75%or more, 80% or more, 85% or more, 90% or more, 95% or more, etc.)surrounds the second electrode. Thus, the first and second electrodes(e.g., cathode and anode, or anode and cathode) may be configured as abullseye pattern; the outer ring may be complete or interrupted (e.g.,allowing electrical connection to the control circuitry). Thus, thefirst (outer ring) electrode may have a much larger area as compared tothe second (inner shape) electrode, such as 2× or more, 3× or more, 3.5×or more, 4× or more, etc. the area of the second electrode. Thisconcentric arrangement, in conjunction with the small maximum diameterof the device, may allow the apparatus to be applied in any orientation.

A wearable neuromodulation apparatus may include: a flexible (e.g.,fibrous) substrate. The fibrous substrate may be a woven (e.g., formedof yarn or other fibers of material) or non-woven (e.g., paper)materials. In some variations, these fibrous substrates may have a shapememory wherein the flexible fibrous substrate is configured to return toa set shape after being folded or bent. Any of these apparatuses mayalso include: a control circuit attached to the fibrous substrate; apower source attached to the fibrous substrate in electricalcommunication with the control circuit; a first electrode on a firstregion of the fibrous substrate, wherein the first electrode comprises afirst conductive gel pad over a first plurality of conductive filamentsattached to the fibrous substrate; a second electrode on a second regionof the fibrous substrate, wherein the second electrode comprises asecond conductive gel pad over a second plurality of conductivefilaments attached to the fibrous substrate; a first electricalconnector coupling the first plurality of conductive filaments to thecontrol circuit; and a second electrical connector coupling the secondplurality of conductive filaments to the control circuit.

The flexible fibrous substrate may be a fibrous polyethyleneterephthalate. In some variations, the flexible fibrous substratecomprises a woven material.

Any of these apparatuses may include a housing enclosing the controlcircuit and coupling the control circuit to the fibrous substrate. Thehousing may mechanically connect a first electrical contact for thecontrol circuit to the first electrical connector and a secondelectrical contact for the control circuit to the second electricalconnector.

Any of these apparatuses may include a control input electricallycoupled to the control circuit and configured to control one or more of:power and intensity of the neuromodulation apparatus.

An outer surface area of the first electrode may be larger than an outersurface area of the second electrode (e.g., the anode may be larger thanthe cathode, or vice-versa).

The plurality of conductive filaments may comprise a mesh of conductivefilaments. For example, the plurality of conductive filaments may beinterwoven into the fibrous substrate. In some variations, the pluralityof conductive filaments comprises a yarn with conductive filaments andinsulating filaments. The plurality of conductive filaments may bestainless steel filaments.

The plurality of conductive filaments may be coupled to the substrate inany appropriate manner, including interweaving, and in some variations,adhesively attaching to the fibrous substrate.

Any appropriate electrical connector may be used. For example, theelectrical connector(s) may comprise one or more of: a conductive yarn,a wire, or a printed electrical trace.

Any of these devices may include a flexible cover over the controlcircuitry. The cover may be formed of the substrate.

For example, described herein are wearable neuromodulation devices thatinclude: a flexible woven substrate; a control circuit attached to thewoven substrate; a power source attached to the woven substrate inelectrical communication with the control circuit; a first electrode ona first region of the woven substrate, wherein the first electrodecomprises a first conductive gel pad over a first plurality ofconductive filaments attached to the woven substrate; a second electrodeon a second region of the woven substrate, wherein the second electrodecomprises a second conductive gel pad over a second plurality ofconductive filaments attached to the woven substrate; a first electricalconnector coupling the first plurality of conductive filaments to thecontrol circuit; and a second electrical connector coupling the secondplurality of conductive filaments to the control circuit.

The woven substrate may comprise a woven insulating material. Forexample, the woven substrate may be woven from a polymeric yarn. In somevariations, the woven substrate is knitted.

The plurality of conductive filaments may comprises a mesh of conductivefilaments; this mesh may be interwoven into the woven substrate and/orattached to the woven substrate. For example, the plurality ofconductive filaments may comprise a yarn with conductive filaments andinsulating filaments.

Any of the apparatuses described herein may be configured aslimited-number-of-use, wearable neuromodulation device that provide apredetermined waveform having a very high electrical efficiency, so thatthe power requirements may be minimized. The limited-number-of-useapplicator apparatus may be configured to provide over x minutes ofelectrical neuromodulation (e.g., 5 min, 7 min, 10 min, 15 min, 20 min,etc.) without requiring recharging, and may include one or more sensors(e.g., impedance sensing circuitry and/or logic) to determine when thedevice is in contact with the skin and ready to apply energy. Forexample, a limited-number-of-use wearable device may include: a flexible(in some variations, fibrous) substrate; a power source above substrate;a control circuit in electrical communication with the power source andconfigured to provide constant current pulsing, further wherein thecontrol circuit comprise a switch configured to generate a DC voltagethat changes amplitude over time to maintain constant current pulsing,the control circuit further comprising an accumulator configured tostore energy from the power source and provide energy for the constantcurrent pulsing; a pair of electrodes on the substrate. In somevariations each electrode may have a conductive gel pad over a pluralityof conductive filaments attached to the substrate. Each electrode may beelectrically coupled to the control circuit via an electrical conductor.The control circuity and/or power source may float relative to thesubstrate (e.g., may not be rigidly connected to it, but allowed to move(though constrained by a cover, such as a fabric cover).

In any of the apparatuses described herein, the power source may be abattery having less than a 50 milliamp hour capacity. For example, thepower source may be one or more alkaline batteries in series having aninstantaneous current output of less than 20 milliamps. In somevariations, the maximum voltage output for the device is between 10 Vand 50 V. In some variations, the power source is a 30 mA*hr (e.g., 30C, 3.7 V) source.

In some variations, the control circuit may be configured to provide anamplitude-modulated carrier waveform having a trapezoidal envelope,wherein the carrier waveform comprises a pair of repeating pulses.

In any of these apparatuses, energy may be accumulated from the batteryand boosted in voltage to provide the constant current pulsing forneuromodulation. For example, the switch may be a switching transistorthat is configured to generate a plurality of kick-up pulses feedinginto an inductor (e.g., accumulator). The inductor may be incommunication with one of the electrodes of the pair of electrodes. Thecontrol circuitry may also include smoothing circuitry to smooth theripples from the kick-up pulsing.

Described herein are wearable neuromodulator apparatuses (e.g., devices)that include: a flexible substrate; a first electrode; a secondelectrode on the flexible substrate; a battery; a control circuitry incommunication with the first electrode and the second electrode; acircuit interrupt removably coupled with the control circuitry, whereinthe circuit interrupt is interposed between the battery and the controlcircuitry so that removing the circuit interrupt powers the controlcircuitry, further wherein the control circuitry is configured todeliver a predefined waveform between the first and second electrodesafter the circuit interrupt is removed, wherein the device weighs 20 gor less.

A wearable neuromodulator device may include a flexible substrate, afirst electrode; a second electrode on the flexible substrate; abattery; a control circuitry, wherein the control circuity has a firstmode of operation in which the battery is disengaged from the controlcircuity and a second mode of operation in which the battery is engagedwith the control circuitry, further wherein the control circuitry isconfigured to deliver a predefined waveform between the first and secondelectrodes when the battery is engaged with the control circuitry,wherein the waveform has a frequency of between 100 Hz and 15 KHz anddelivers a charge per phase of between 0.1-10 microCoulombs; and acircuit interrupt removably coupled with the control circuitry andconfigured to switch the control circuitry from the first mode to thesecond when the circuit interrupt is removed.

In any of the apparatuses described herein the circuit interrupt may bea pull tab, pull pin, etc. and may be formed of a material that iselectrically insulating and prevents electrical contact between thebattery and the control circuitry. For example, the pull tab or pin mayinterrupt the circuitry by holding apart a biased contact that isreleased when the interrupt is pulled out, allowing the circuit to closeand power to be applied to the control circuit.

In any of these apparatuses, the first electrode may comprise a firstadhesive hydrogel and the second electrode may comprise a secondadhesive hydrogel.

As mentioned above, any of these apparatuses may weight 20 g or less(e.g., 15 g or less, 10 g or less, etc.) which may allow the device tobe worn just by the adhesive properties of the standard electricallyconductive hydrogel without disrupting the electrical contact betweenthe skin and the hydrogel. Any of these apparatuses may have a maximumdiameter of 10 cm or less (e.g., 9 cm or less, 8 cm or less, 7 cm orless, 6 cm or less, etc.), and an average or maximum thickness of 1 cmor less (e.g., 0.8 cm or less, 0.7 cm or less, 0.6 cm or less, 0.5 cm orless, etc.).

As mentioned, any of these apparatuses may include a flexible coverwherein the battery and control circuitry are between the flexible coverand the flexible substrate. The flexible cover may be a fabric.

In any of these apparatuses, the control circuitry may be configured togenerate and deliver the pre-defined waveform between the first andsecond electrodes when the battery is engaged with the control circuitryand an impedance between the first and second electrodes is within apre-defined range (e.g., indicating that the device is being worn onskin). The predefined waveform is configured to run for 25 minutes orless (e.g., 20 min or less, 15 min or less, 10 min or less, 5 min orless, between 3-25 min, between 3-20 min, between 3-15 min, between 3-10min, etc.).

As discussed above, in general, any of these apparatuses may not includeany user inputs or controls other than the circuit interrupt.Specifically, and of these apparatuses may not include a control (e.g.knob, dial, button, slider, etc.) or input for adjusting the waveform.The waveform may be preloaded into the apparatus.

As mentioned above, in any of these apparatuses, the waveform may have afrequency of between about 100 Hz and 1.6 KHz; the waveform may have acharge per phase of between about 0.1-5 μC/phase; and the waveform mayhave a DC percentage of between 80-100%. In any of these apparatuses andmethods the waveform may have a current of between about 1 and 20 mA.

In any of these apparatuses, the circuit interrupt may be removable fromthe apparatus. For example, the circuit interrupt may be a pull tab orpin that is removable from the apparatus after it is removed from thepackaging but before it is applied to the skin.

For example, a wearable neuromodulator device may include: a flexiblesubstrate; a first electrode on the flexible substrate; a secondelectrode on the flexible substrate; a battery; a control circuitry,wherein the control circuity has a first mode of operation in which thebattery is disengaged from the control circuity and a second mode ofoperation in which the battery is engaged with the control circuitry,further wherein the control circuitry is configured to deliver apre-defined waveform between the first and second electrodes when thebattery is engaged with the control circuitry and an impedance betweenthe first and second electrodes is within a pre-defined range, whereinthe waveform has a frequency of between 100 Hz and 15 KHz and delivers acharge per phase of between 0.1-10 microCoulombs; and a pull tabremovably coupled with the control circuitry and configured to switchthe control circuitry from the first mode to the second when the pulltab is pulled, wherein the device weighs 20 g or less.

A wearable neuromodulator device, the device comprising: a flexiblesubstrate; a first electrode on the flexible substrate; a secondelectrode on the flexible substrate; a battery; a control circuitry,wherein the control circuity has a first mode of operation in which thebattery is disengaged from the control circuity and a second mode ofoperation in which the battery is engaged with the control circuitry,further wherein the control circuitry is configured to deliver apre-defined waveform between the first and second electrodes when thebattery is engaged with the control circuitry and an impedance betweenthe first and second electrodes is within a predefined range, whereinthe waveform has a frequency of between 100 Hz and 15 KHz and delivers acharge per phase of between 0.1-10 microCoulombs; a cover covering theflexible substrate so that the battery and control circuitry areenclosed between the cover and the flexible substrate, wherein thethickness of the device between the cover and the flexible substrate isless than 5 mm; and a pull tab removably coupled with the controlcircuitry and configured to switch the control circuitry from the firstmode to the second when the pull tab is pulled, wherein the device has aprinciple diameter that is between 2 cm and 10 cm.

Any of these apparatuses (limited-number-of-use apparatuses) may beconfigured for two or more uses. For example, a wearable neuromodulatordevice may include: a flexible substrate; a first electrode and a secondelectrode on the flexible substrate; a first hydrogel layer inelectrical communication with the first electrode and a second hydrogellayer in electrical communication with the second electrode; a thirdhydrogel layer in electrical communication with the first hydrogellayer; a removable release layer, wherein the first hydrogel layer isseparated from the third hydrogel layers by the release layer; abattery; a control circuitry; and a circuit interrupt removably coupledwith the control circuitry, wherein the circuit interrupt is interposedbetween the battery and the control circuitry so that removing thecircuit interrupt powers the control circuitry, further wherein thecontrol circuitry is configured to deliver a first predefined waveformbetween the first and second electrodes after the circuit interrupt isremoved, and a second predefined waveform between the first and secondelectrodes after the release layer is removed. As mentioned above, therelease layer may be coupled to the control circuitry.

In any of these apparatuses, the control circuitry may be configured todeliver the first predefined waveform between the first and secondelectrodes after the circuit interrupt is removed and an impedancebetween the first and second electrodes is within a predefined range,and the second predefined waveform between the first and secondelectrodes after the release layer is removed and the impedance betweenthe first and second electrodes is within the predefined range.

In some variations the first predefined waveform is the same as thesecond predefined waveform. Alternatively, in some variations, thesecond predefined waveform has an intensity that is between 5-50% lowerthan the first predefined waveform. The first predefined waveform may beconfigured to run for between 4-25 minutes.

In any of these apparatuses, the control circuitry may be configured tostop delivering the first or second predefined waveform if the impedancebetween the first and second electrode is outside of the predefinedrange. Thus, the apparatus may be configured to periodically and/orcontinuously monitor the impedance between the electrodes to confirmthat the device is on the skin (e.g., every 1 ms, every 5 ms, every 10ms, every 20 ms, every 50 ms, every 100 ms, etc.).

The control circuitry may be configured so that the first predefinedwaveform and the second predefined waveform each comprise a constantcurrent and a variable voltage.

As mentioned above, the release layer may comprise a plurality ofopenings therethrough to permit electrical contact between the firsthydrogel and the third hydrogel. These openings may be shaped (e.g.,round, triangular, etc.) and may be oriented to assist in removing therelease layer from an underlying layer of hydrogel. The release layermay be an insulating material; in some variations the release layer isinstead an electrically conductive material (e.g., the release layer maybe formed of an electrical insulating material impregnated withconductive particles, etc.). Typically, the release layer comprises anon-stick or low-stick material (e.g., a waxed material, etc.).

For example, a wearable neuromodulator device may include: a flexiblesubstrate; a first electrode and a second electrode on the flexiblesubstrate; a first hydrogel layer in electrical communication with thefirst electrode and a second hydrogel layer in electrical communicationwith the second electrode; a third hydrogel layer in electricalcommunication with the first hydrogel layer; a fourth hydrogel layer inelectrical communication with the second hydrogel layer; a removablerelease layer, wherein the first and second hydrogel layers areseparated from the third and fourth hydrogel layers by the releaselayer; a battery; a control circuitry; and a pull tab removably coupledwith the control circuitry, wherein the pull tab is interposed betweenthe battery and the control circuitry so that removing the pull tabpowers the control circuitry, further wherein the control circuitry isconfigured to deliver a first predefined waveform between the first andsecond electrodes after the pull tab is removed, and a second predefinedwaveform between the first and second electrodes after the release layeris removed, wherein the second predefined waveform has an intensity thatis between 5-50% lower than the first predefined waveform.

Any of these apparatuses may include a fabric cover material, asdescribed above. For example, a wearable neuromodulator device mayinclude: a flexible substrate; a first electrode; a second electrode onthe flexible substrate; a battery; a control circuitry coupled to thefirst electrode and the second electrode, wherein the control circuitryis configured to deliver a predefined waveform between the first andsecond electrodes when the battery is powering the control circuitry;and an elastic cover wherein the battery and control circuitry arebetween the cover and the flexible substrate, further wherein the deviceweighs 20 g or less, has a maximum thickness of 7 mm or less, and amaximum diameter of 10 cm or less. The elastic cover may comprise anelastomeric fabric, e.g., an elastomeric cotton. The elastic cover maycomprise a nonwoven elastomeric material. In some variations the batteryand control circuitry are at least partially wrapped in the elasticcover.

The elastic cover may be secured over the flexible substrate, e.g., theelastic cover may be adhesively secured to the flexible substrate. Anyof these apparatuses may include a frame securing the battery and thecontrol circuitry, wherein the frame is covered by the elastic cover.

A wearable neuromodulator device may include: a flexible substrate; afirst electrode on the flexible substrate; a second electrode on theflexible substrate; a battery; a control circuitry coupled to the firstelectrode and the second electrode, wherein the control circuitry isconfigured to deliver a predefined waveform between the first and secondelectrodes when the battery is powering the control circuitry; and anelastic cover comprising an elastomeric fabric that is adhesivelysecured to the flexible substrate wherein the battery and controlcircuitry are at least partially wrapped in the cover. The device mayweighs 20 g or less, have a maximum thickness of 7 mm or less, and amaximum diameter of 10 cm or less.

A wearable neuromodulator device may include: a flexible substrate; afirst electrode that is concentrically arranged around a secondelectrode, wherein the first and second electrodes are on the flexiblesubstrate; a battery; a control circuitry coupled to the first electrodeand the second electrode, wherein the control circuitry is configured todeliver a predefined waveform between the first and second electrodeswhen the battery is powering the control circuitry; and an elastic coverattached to the flexible substrate, wherein the battery and controlcircuitry are between the cover and the flexible substrate, furtherwherein the device weighs 20 g or less.

The first electrode may completely surround the second electrode; insome variations the first electrode surrounds more than 75% (e.g., 80%,85%, 90%, etc.) of the second electrode, as described above. The firstelectrode may be configured as a cathode and the second electrode may beconfigured as an anode. The predefined waveform may be configured to runfor 15 minutes or less.

A wearable neuromodulator device may include: a flexible substrate; afirst electrode comprising a first hydrogel; a second electrodecomprising a second hydrogel, wherein the first electrode isconcentrically arranged around the second electrode, further wherein thefirst and second electrodes are on the flexible substrate; a battery; acontrol circuitry coupled to the first electrode and the secondelectrode, wherein the control circuitry is configured to deliver apredefined waveform between the first and second electrodes when thebattery is powering the control circuitry and an impedance between thefirst and second electrodes is within a predefined range, furtherwherein the waveform has a frequency of between 100 Hz and 15 KHz anddelivers a charge per phase of between 0.1-10 microCoulombs; and anelastic cover attached to the flexible substrate, wherein the batteryand control circuitry are between the cover and the flexible substrate,further wherein the device weighs 20 g or less.

Any of these methods and apparatuses may be configured to deliver apendulum waveform, as described above. For example, a wearableneuromodulator device may include: a flexible substrate; a firstelectrode; a second electrode on the flexible substrate; a battery; acontrol circuitry coupled to the first electrode and the secondelectrode, wherein the control circuitry is configured to deliver apredefined waveform between the first and second electrodes when thebattery is powering the control circuitry, further wherein thepredefined waveform has a frequency of between 100 Hz and 15 KHz, a dutycycle of between 1% and 50% and a charge per phase of between 0.1-10microCoulombs, further wherein the waveform oscillates one or more offrequency, center amplitude or center duty cycle with an oscillationfrequency of between about 2-20 seconds; and a cover wherein the batteryand control circuitry are between the cover and the flexible substrate.The predefined waveform may be biphasic or monophasic.

A wearable neuromodulator device may include: a flexible substrate; afirst electrode on the flexible substrate; a second electrode on theflexible substrate; a battery; a control circuitry coupled to the firstelectrode and the second electrode, wherein the control circuitry isconfigured to deliver a predefined waveform between the first and secondelectrodes when the battery is powering the control circuitry, furtherwherein the predefined waveform has a frequency of between 100 Hz and 2KHz, a duty cycle of between 1% and 50% and a charge per phase ofbetween 0.4-4 microCoulombs, further wherein the waveform oscillates oneor more of frequency, center amplitude or center duty cycle with anoscillation frequency of between about 2-20 seconds; and a cover whereinthe battery and control circuitry are between the cover and the flexiblesubstrate.

Also described herein are methods of using any of the apparatusesdescribed herein, including methods of using them for one or moreindications, such as to induce a energized state in the user, to inducea relaxed state in the user, to improve a cognitive state (e.g., toenhance or improve memory), to treat a disorder, including ADHD,neurogenic inflammation, autoimmune disorders such as psoriasis, generalanxiety disorders, sleep-related disorders (e.g. insomnia, etc.) and/orimproving sleep (including but not limited to increasing sleep duration,reducing sleep onset, etc.).

For example described herein are methods of operating or applying aneuromodulator (neuromodulator) as described herein. A method mayinclude: engaging a battery of a wearable neuromodulator device with acontrol circuitry of the wearable neuromodulator device when a circuitinterrupt of a wearable neuromodulator device is removed; delivering apre-defined waveform between a first electrode and a second electrodewhen the battery is engaged with the control circuitry and an impedancebetween the first and second electrodes is within a pre-defined rangeindicating that the device is place on a skin surface; and stoppingdelivery of the pre-defined waveform when the impedance between thefirst and second electrodes is outside of the pre-defined range or whenthe waveform is complete. The method may include a method of inducing anenergized cognitive state in the subject, a method of enhancing thesubject's sympathetic nervous system, a method of relaxing thesubject/inducing relaxation, a method of enhancing cognition (e.g.,memory), a method of treating a disorder such as general anxietydisorder, ADHD, rheumatoid arthritis, psoriasis, a method of treating asleep-related disorder, etc.

Any of these methods may include removing the apparatus from a packaging(e.g., a foil package), removing an adhesive backing over the hydrogelportion of the electrodes, and/or placing the wearable neuromodulatordevice onto a subject's skin. For example, placing the device on thesubject's neck (e.g., on a central region of the subject's neck, on aside of the subject's neck/behind the subject's ear), or on thesubject's forehead. The device may be configured to be retained on theskin by just the electrode hydrogel (without requiring any additionaladhesive or securement such as a strap, etc.). For example, the devicemay weigh 20 g or less, have a maximum diameter of 10 cm or less, and/ora maximum thickness of 1 cm or less. Placing the device may comprisesbending the device to fit the subject's skin, further wherein the devicemay include a flexible cover over a battery and the control circuitry,so that the battery and control circuitry are between the flexible coverand a flexible substrate holding the first electrode and the secondelectrode (e.g., the flexible cover may be a fabric, as describedabove). The predefined waveform may be configured to run for 25 min orless (e.g., 20 minutes or less, 15 minutes or less, 10 minutes or less,7 minutes or less or 5 minutes or less, 4 minutes or less etc.). Asmentioned, the device may not include any user inputs or controls otherthan the circuit interrupt. Any of these methods may include removingthe circuit interrupt from the device. Removing the device from the skinmay cause the device to go into a standby mode or a locked mode in whichthe waveform is not applied.

For example, a method of inducing an energized state in a subject mayinclude: placing a wearable neuromodulator device onto the subject'sneck so that a first electrode and a second electrode contact thesubject's skin, wherein the wearable neuromodulator device weights 20 gor less; engaging a battery of the wearable neuromodulator device with acontrol circuitry of the wearable neuromodulator device when a circuitinterrupt of a wearable neuromodulator device is removed; delivering apre-defined waveform between the first and second electrodes when thebattery is engaged with the control circuitry and an impedance betweenthe first and second electrodes is within a pre-defined range indicatingthat the device is place on a skin surface, wherein the waveform has afrequency of between 100 Hz and 15 KHz and delivers a charge per phaseof between 0.1-5 microCoulombs; and automatically stopping delivery ofthe pre-defined treatment plan when the impedance between the first andsecond electrodes is outside of the pre-defined range or when thewaveform is complete.

Any of these methods may include using pendulum waveforms. For example,a method may include: placing a wearable neuromodulator device onto asubject's skin; delivering a pre-defined waveform between the first andsecond electrodes when an impedance between a first electrode and asecond electrode is within a pre-defined range indicating that thedevice is place on a skin surface, wherein the waveform has a frequencyof between 100 Hz and 15 KHz, a duty cycle of between 1% and 50% and acharge per phase of between 0.1-5 microCoulombs, further wherein thewaveform oscillates one or more of frequency, center amplitude or centerduty cycle with an oscillation frequency of between about 2-20 seconds;and automatically stopping delivery of the pre-defined treatment planwhen the impedance between the first and second electrodes is outside ofthe pre-defined range or when the waveform is complete.

A method of inducing an energized state in a subject may include:placing a wearable neuromodulator device onto the subject's neck so thata first electrode and a second electrode contact the subject's skin;delivering a pre-defined waveform between the first and secondelectrodes when an impedance between the first and second electrodes iswithin a pre-defined range indicating that the device is place on a skinsurface, wherein the waveform has a frequency of between 100 Hz and 15KHz, a duty cycle of between 1% and 50% and a charge per phase ofbetween 0.1-5 microCoulombs, further wherein the waveform oscillates oneor more of frequency, center amplitude or center duty cycle with anoscillation frequency of between about 2-20 seconds; and automaticallystopping delivery of the pre-defined treatment plan when the impedancebetween the first and second electrodes is outside of the pre-definedrange or when the waveform is complete.

A method of inducing a relaxed cognitive state in a subject may include:placing a wearable neuromodulator device onto the subject's neck so thata first electrode and a second electrode contact the subject's skin;delivering a pre-defined waveform between the first and secondelectrodes when an impedance between the first and second electrodes iswithin a pre-defined range indicating that the device is place on a skinsurface, wherein the waveform has a frequency of between 1 KHz and 15KHz, a duty cycle of between 1% and 50% and a charge per phase ofbetween 0.1-5 microCoulombs, further wherein the waveform oscillates oneor more of frequency, center amplitude or center duty cycle with anoscillation frequency of between about 2-20 seconds; and automaticallystopping delivery of the pre-defined treatment plan when the impedancebetween the first and second electrodes is outside of the pre-definedrange or when the waveform is complete.

A method of enhancing relaxation may include: placing a wearableneuromodulator onto a back of a subject's neck; removing a circuitinterrupt of the wearable neuromodulator to engage a battery of awearable neuromodulator with a control circuitry of the wearableneuromodulator; delivering a pre-defined waveform between a firstelectrode and a second electrode when the battery is engaged with thecontrol circuitry and an impedance between the first and secondelectrodes is within a pre-defined range indicating that the device isplace on a skin surface, wherein the pre-defined waveform has charge perphase of between 0.1-10 microCoulombs; and stopping delivery of thepre-defined waveform when the impedance between the first and secondelectrodes is outside of the pre-defined range or when the waveform iscomplete. Placing the wearable neuromodulator may comprise placing thedevice on central region of the back of the subject's neck. Thepre-defined waveform may have a frequency of between 1 KHz and 18 KHz.The pre-defined waveform may have a charge per phase of between 0.1-1.2μC. The pre-defined waveform may have a DC percentage of between70-100%.

As mentioned, also described herein are techniques for enhancing sleep(reducing sleep latency, increasing time asleep, etc.), as well asmethods of treating certain auto-immune disorders such as psoriasis. Forexample, described herein are method of enhancing sympathetic nervoussystem activity to treat psoriasis, the method comprising: placing awearable neuromodulator on a the subject having psoriasis; removing acircuit interrupt of the wearable neuromodulator to engage a battery ofa wearable neuromodulator with a control circuitry of the wearableneuromodulator; reducing the subject's psoriasis by automaticallydelivering a pre-defined waveform between a first electrode and a secondelectrode when the battery is engaged with the control circuitry and animpedance between the first and second electrodes is within apre-defined range indicating that the device is place on a skin surface,wherein the pre-defined waveform has charge per phase of between 0.1-10microCoulombs; and stopping delivery of the pre-defined waveform whenthe impedance between the first and second electrodes is outside of thepre-defined range or when the waveform is complete.

Also described herein are methods and apparatuses of enhancing orimproving memory. Any of the apparatuses and features described abovemay be adapted as described herein for enhancing memory. For example,any of these apparatuses may include an additional electrode that may beseparately positioned relative to the first and second electrode. Inparticular the first and second electrode of the body of the apparatusmay be positioned over the subject's temple (on the side of theforehead) while the third electrode, e.g., cathode, may be positionedover the midline of the forehead. Thus the apparatus may include anextension arm that is between about 1-4 inches (e.g., between about 1-3inches, between about 1-2.2 inches) from the edge of the concentricelectrodes on the substrate. The extension arm may be formed of thesubstrate, which may be a flexible material (e.g., a flexible polymer,fabric, etc., as described herein). The control circuitry may apply thesame pre-defined waveform to both the first and second and third (orthird and second) electrodes, in a synchronous manner.

For example, a method of enhancing cognition may include: placing awearable neuromodulator device weighing 20 g or less onto a subject'shead; delivering, from a processor within the wearable device, apre-defined waveform between a first electrode and a second electrodewhen an impedance between the first electrode and the second electrodeis within a pre-defined range indicating that the device is on a skinsurface, wherein the waveform has charge per phase of between 0.1-10microCoulombs; and automatically stopping delivery of the pre-definedtreatment plan when the impedance between the first and secondelectrodes is outside of the pre-defined range or when the waveform iscomplete.

As in any of the methods of use described herein, placing may compriseconforming the wearable neuromodulator device to the subject's head byallowing a flexible fabric cover over the wearable device to stretch.Similarly, delivering may comprise automatically delivering thepredefined waveform without the subject operating a control or adjustingthe predefined waveform. The method of enhancing cognition may compriseenhancing memory. Placing may comprise placing the first and secondelectrode over the subject's temple and placing a third electrode in amiddle portion of the subject's forehead. The first and secondelectrodes may be placed on the subject's temple and forehead. Thewaveform may comprises a frequency of between about 4-8 Hz.

For example, a method of enhancing cognition, including memory mayinclude: placing a wearable neuromodulator device weighing 20 g or lessonto a subject's temple and forehead; automatically delivering, from aprocessor within the wearable device, a pre-defined waveform from afirst electrode on the subject's temple and second electrode on thesubject's forehead, when an impedance measured at either or both thefirst and second electrodes is within a pre-defined range indicatingthat the device is on a skin surface, wherein the pre-defined waveformhas charge per phase of between 0.1-10 microCoulombs and comprises afrequency of between about 4-8 Hz; and automatically stopping deliveryof the pre-defined treatment plan when the impedance is outside of thepre-defined range or when the waveform is complete.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe claims that follow. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings of which:

FIG. 1 is one example of a limited-number-of-use, wearableneuromodulator (e.g., neuromodulator) having a flexible (e.g., woven)substrate including control circuitry and electrodes; the cover is alsoformed of a flexible fabric.

FIGS. 2A-2B show another example of a limited-number-of-use wearableneuromodulator configured to be worn behind a user's ear.

FIG. 3 is a table illustrating the relationship between gel padthickness and distance to a target nerve within the body.

FIGS. 4A-4B illustrate examples of electrodes (e.g., anode and cathode,primary and return) including a gel pad region overlaying a plurality ofcurrent-distributing conductive fibers (e.g., stainless steel fibers)between the substrate and the conductive gel pads.

FIG. 4C shows examples of electrode shapes that may be used, includingfor use with a behind-the-ear (e.g., mastoid) electrode.

FIGS. 5A and 5B illustrate another example of a pair of electrodes(e.g., (e.g., anode and cathode, primary and return) that may be used,e.g., as part of a limited-number-of-use, wearable neuromodulatorconfigured to be worn on a user's neck.

FIG. 6A is an exemplary schematic section through a protective frame(e.g., housing) for a control circuit and/or battery of alimited-number-of-use, wearable neuromodulator.

FIGS. 6B-6E illustrate examples of connections that between a conductor(e.g., conductive yarn) and an electrical contact (pad) of a controlcircuit, including within a protective frame or housing.

FIG. 7 is an example of a schematic of another example of alimited-number-of-use, wearable neuromodulator having a flexible (e.g.,woven) substrate including control circuitry and electrodes. In FIG. 7,the wearable neuromodulator may be worn on the back of the user's neck.

FIGS. 8A-8F illustrate different layers of the exemplary apparatus shownin FIG. 7, showing exemplary dimensions (which may be +/−5%, 10%, 15%,etc.).

FIG. 9 illustrates one method of fabricating a limited-number-of-use,wearable neuromodulator having a flexible (e.g., woven) substrateincluding control circuitry and electrodes such as the one shown in FIG.7.

FIG. 10A is an example of a fibrous material including one or moreconductive filament(s) that may be used as part of alimited-number-of-use, wearable neuromodulator having a flexible fibrous(e.g., woven) substrate.

FIG. 10B is a schematic example of a woven material including bothinsulative strands and conductive strands, interwoven.

FIG. 11 is an example of a woven material having an interwovenconductive filaments making electrical contact with a bundle ofconductive fibers (e.g., in a yarn or wire). In some variations theconductive filaments from the bundle may be continuous with theinterwoven conductive filaments in the woven substrate.

FIG. 12 illustrates an example of a method of manufacturing alimited-number-of-use, wearable neuromodulator having a flexible wovensubstrate. In FIG. 12, a plurality of adjacent wearable devices arefabricated in a single layer that is then cut or otherwise divided intoseparate devices.

FIG. 13 illustrates one method of connecting a conductive yarn (e.g.,including one or more stainless steel filaments) to a flexible, e.g.,woven, substrate.

FIG. 14 illustrates an example of a woven material (e.g., wovenpolymeric material) to which a plurality of conductive filaments (e.g.,stainless steel filaments) is coupled.

FIG. 15A is a sectional view through a portion of an electrode of alimited-number-of-use, wearable neuromodulator having a flexiblesubstrate.

FIG. 15B show an enlarged view through a section of a conductive yarnincluding stainless steel fibers that may form part of an electrode,such as the one shown in FIG. 15A.

FIG. 16 is an example of a section through a limited-number-of-use,wearable neuromodulator having a flexible woven substrate showing acontrol circuit (circuitry) within a protective housing, electricalconnections (e.g., via conductive yarns) to electrodes on the flexiblesubstrate.

FIG. 17 schematically illustrates an example of a limited-number-of-use,wearable neuromodulator having a flexible woven substrate in which ahousing enclosing the control circuit also forms a control (e.g.,button) that may be actuated by the wearer/user.

FIG. 18 is a schematic illustration of another example of alimited-number-of-use, wearable neuromodulator having a flexible wovensubstrate in which the housing holding the control circuit(s) is sewnonto the substrate.

FIG. 19 is a schematic illustration of another example of alimited-number-of-use, wearable neuromodulator having a flexible wovensubstrate in which the housing holding the control circuit(s) is sewnonto the substrate via an electrically conductive yarn or filament thatcan make electrical connection to one or more electrode(s).

FIG. 20 is a schematic illustration of another example of alimited-number-of-use, wearable neuromodulator having a flexiblesubstrate including a cover that may be a separate and/or differentfabric material (shown as a woven material in this example).

FIG. 21 is a schematic illustration of another example of alimited-number-of-use, wearable neuromodulator having a flexible wovensubstrate including an elastomeric fabric cover (elastomer bag).

FIG. 22 illustrates an example of a woven stainless-steel that is boththe connector to the control circuitry and also extends radially outwardto form a conductive mesh within the electrode underneath a conductivegel pad.

FIG. 23 is another example of a limited-number-of-use, wearableneuromodulator having a flexible woven substrate.

FIG. 24A is another example of a limited-number-of-use, wearableneuromodulator having a flexible woven substrate configured to be wornbehind the user's ear.

FIG. 24B shows the device of FIG. 24A in the fully-assembledconfiguration, folded over itself.

FIGS. 25A and 25B illustrate an example of a flexible fibrous substratehaving a shape memory wherein the flexible fibrous substrate isconfigured to return to a set shape after being folded or bent. In FIG.25A the apparatus is folded/bent, while in FIG. 25B the apparatus isshown returning to its shape.

FIG. 26 illustrates one example of the relationship between current andvoltage during the application of energy by a limited-number-of-use,wearable neuromodulator as described herein.

FIG. 27 is an exemplary circuit diagram for one variation of alimited-number-of-use, wearable neuromodulator as described herein.

FIG. 28 show and example of a voltage ramp for a boost converter of alimited-number-of-use, wearable neuromodulator as described herein.

FIG. 29 is an exemplary circuit diagram for another variation of alimited-number-of-use wearable neuromodulator as described herein.

FIG. 30A is a table illustrating exemplary descriptors for anamplitude-modulated carrier waveform having a trapezoidal envelope,wherein the carrier waveform comprises a pair of repeating pulses; thesewaveforms may be delivered by a limited-number-of-use wearableneuromodulator as described herein.

FIG. 30B is a table (table 3) illustrating parameters for exemplaryneuromodulation as described herein.

FIGS. 31A-31H illustrate one example of a limited-number-of-use wearableneuromodulator as described herein. FIG. 31A is a top view, FIG. 31B isa bottom view, FIG. 31C is a top perspective view, FIG. 31D is a bottomperspective, FIG. 31E is a left side view, FIG. 31F is a front view,FIG. 31G is a right side view, FIG. 31H is a left side view, and FIG.31I is a back view.

FIGS. 32A-32H illustrate one example of a limited-number-of-use wearableneuromodulator as described herein, having multiple layers of hydrogeland a release layer, configured to allow more than one use. FIG. 32A isa top view, FIG. 32B is a bottom view, FIG. 32C is a top perspectiveview, FIG. 32D is a bottom perspective, FIG. 32E is a left side view,FIG. 32F is a front view, FIG. 32G is a right side view, FIG. 32H is aleft side view, and FIG. 32I is a back view.

FIGS. 33A and 33B illustrate one example of prototype of alimited-number-of-use neuromodulator as described herein.

FIG. 34A is an exploded view of one variation of a limited-number-of-useneuromodulator as described herein.

FIG. 34B is another example of an exploded view of the apparatus of FIG.34A.

FIG. 34C is an example showing two layers of hydrogel separated by arelease layer

FIGS. 35A and 35B illustrates one method of wrapping a fabric cover overa battery and control circuitry.

FIG. 36 is an example of one variation of a limited-number-of-useneuromodulator apparatus as described herein, including two layers ofhydrogel separated by a release layer (shown without a fabric cover).

FIGS. 37A and 37B illustrate examples of a limited-use neuromodulatorsas described herein.

FIG. 38A is an exemplary method of using a limited-use neuromodulatorsas described herein.

FIG. 38B illustrates the location of the application of a neuromodulatorfor inducing an energized cognitive state.

FIG. 39A-39C illustrates one method of removing a used layer of hydrogelby pulling on a release layer.

FIG. 39D illustrate an example of a neuromodulator and packaging (e.g.,foil packet).

FIG. 40 is one example of a partial view of a neuromodulator including apair of concentrically arranged electrode (electrode trace andconductive and adhesive hydrogel, each connected to a controlcircuitry).

FIG. 41 is an example of a release layer (configured as two separaterelease layers) for use with a neuromodulator apparatus as describedherein.

FIGS. 42-46 illustrate one method of forming a limited-number-of-useneuromodulator apparatus with a pair of release layers. FIG. 42 showsplacement of a first release layer on the second (inner) electrode;FIGS. 43 and 44 show placement of the outer release layer on the first(outer) electrode that is concentrically around the second electrode.FIG. 45 illustrates placement of a second gel layer for the second(inner) electrode. FIG. 46 shows placement of the second gel layer forthe first (outer) electrode.

FIG. 47 illustrates the example the assembled limited-number-of-useneuromodulator apparatus assembled as shown in FIGS. 42-46. Thisvariation includes multiple (e.g., 2) layers of conductive gel; afterthe first use a layer of the gel may be removed, leaving the fresh underlayer. In this example, separate pull-tabs may remove the inner andouter gel regions after use; these may be combined into a single releaselayer.

FIGS. 48 and 49 illustrate examples of pendulum waveforms that may beused with a strong (FIG. 48) and mild (FIG. 49) stimulation waveforms.

FIG. 50 is another example of a limited-number-of use neuromodulator asdescribed herein.

FIG. 51 is an example prototype of a neuromodulator formed of a wovenmaterial (in this example a stainless steel yarn) having electrodesformed one a woven substrate.

FIG. 52A is an example of a test of a woven electrode similar to thevariation shown in FIG. 51. FIG. 52B illustrates transmission of a testwaveform using the prototype neuromodulator shown in FIG. 52A.

FIG. 53 is a prototype of an alternative design of a neuromodulatorsimilar to that shown in FIG. 51, having electrodes formed one a wovensubstrate.

FIG. 54 is a prototype of an alternative design of a neuromodulatorsimilar to that shown in FIG. 51, having electrodes formed one a wovensubstrate.

FIG. 55 is another example of a prototype of an alternative design of aneuromodulator having electrodes formed one a woven substrate, similarto that shown in FIG. 51.

FIGS. 56A-56B is one example of a neuromodulator similar to thosedescribed above (e.g., in FIGS. 31A-31H and 32A-32H, configured to havea third electrode (e.g., cathode). FIG. 56A shows the neuromodulatorfrom the front (showing the fabric cover wrapping around and coveringthe battery and control circuitry, while FIG. 56B shows theneuromodulator from the back, showing the electrodes (including thehydrogel forming the electrodes).

FIG. 57 shows one example of a subject wearing a neuromodulator such asthe one shown in FIGS. 56A-56B for enhancing memory.

FIG. 58 illustrates the approximate placement of the electrodes over thetarget brain regions for enhancing memory as described herein.

FIG. 59 illustrate brain regions corresponding to the application ofelectrical energy received by the subject using the neuromodulatorapparatus shown in FIGS. 56A-56B and 57 when a waveform configured forenhancing memory (e.g., having a frequency component between about 4-8Hz) is applied.

DETAILED DESCRIPTION

The apparatuses described herein include limited-number-of-useneuromodulators that may be comfortably worn on the skin of a user tonon-invasively apply transdermal electrical stimulation (TES). Theseapparatuses may be formed of a soft, compliant material, and may have asimplified user interface, which may not include any buttons orcontrols; these apparatuses (e.g., devices and systems, includingneuromodulators) may be configured to run autonomously once applied.These apparatuses may also include improved power management features.

For example, any of these apparatuses may be configured to provideneuromodulation by applying a series of constant-current electricalpulses that change as a function of time to modulate the neuralactivities. This weight, size, simplicity of use as well as theparameters of the constant current pulses disclosed herein are specificto these apparatuses and may distinguish from otherneurostimulators/neuromodulators, including muscle stimulators or TENSdevices.

A limited-number-of-use apparatus as disclosed here may comprise two ormore conductive gel (e.g. hydrogel) layers or pads that may form part ofthe electrodes, e.g., anode and cathode, and may be characterized byparticular parameters for neuromodulation using these apparatuses.Specifically, the conductive gel pads used in any of the apparatusesdescribed herein may be within a specific range of thicknesses, surfaceareas, and shapes. These parameters have been determined (after numeroustrials) and are specific for the anatomy at the location of attachment.

In general, the apparatuses described herein may include a fabricmaterial forming all or part of the apparatus, including the cover, asubstrate onto which the electrodes are formed and/or the electrodesthemselves. Thus, any of the apparatuses described herein may beself-contained, including a substrate (including a polymeric and/orwoven substrate, as described below), on which two or more electrodesand/or gel pads connect via a flexible connector to control circuitryand a power source (e.g., battery) which may be attached to the body ofthe substrate or may ‘float,’ and be freely moveable relative to thesubstrate. The control circuitry may be pre-configured to include thetreatment waveform(s) for applying a predetermined neuromodulationpattern. The entire structure may be flexible, and may be applied to anyappropriate region of the body, but particularly the head, neck, etc.

Woven Substrates

In some, but not all, of the variations described herein the substratemay be a woven substrate. For example, FIG. 1 illustrates a firstexample of a limited-number-of-use neuromodulator apparatus. In FIG. 1,the substrate is a woven fabric 115 onto which all of the components ofthe system have been added. For example, the limited-number-of-useneuromodulator 100 includes two gel pads 103, 119, each positioned overan electrode 121, 123, (or forming part of the electrode) and eachconnected, via a flexible conductor (e.g., conductive trace 109, 117) toa control circuitry 113 and power supply 111. In this example, theneuromodulator includes a control button 107 that may be used to turnon/off the device and/or adjust the intensity and/or pause/stop theapplication of neuromodulation. As will be described in greater detailbelow, in some variations no additional button or control is included.

Any appropriate knitted or woven substrate may be used. For example, thesubstrate may be a blend conductive and insulating yarns of manyvarieties to enable the apparatus to be ‘knit to shape’. As used herein,the term woven may be used generically to materials formed of one ormore fibers or group of fibers (e.g., cables, filaments, threads, yarns,etc.). A knitted material is typically formed of a single strand(monofilament, poly-filament, etc.); other woven materials may be formedof multiple strands.

The apparatus shown in FIG. 1 may be adapted for use to the head (e.g.,between the region behind the ear, such as the mastoid, and the neck, orbehind the ear/mastoid and the temple. In use, the apparatus may beapplied to the skin with the first end (e.g., gel pad 103) applied toone region, such as the mastoid region, and the second end (e.g., gelpad 119) applied to a second region, such as the neck (e.g., midline ofthe back of the user's neck) or in some variations, the temple. Thesubstrate material may be soft and flexible, permitting the apparatus toconform comfortably to the subject's skin.

FIGS. 2A-2B illustrate another variation of an apparatus as describedherein. In this example, the apparatus is configured to be alimited-number-of-use device that can be worn behind the user's ear.FIG. 2A shows an example of a printed device structure before folding(along the fold 205) into a finished device. This configuration may bebehind the ear (e.g. mastoid) and may provide an “energy” (stimulating)effect in the user. In FIG. 2A, the oval gel pad 207 is configured tosit on top of a bony structure behind the user's ear. The partiallyconcentric reference electrode 209 may at the neck around the bottom ofthe user's ear when the apparatus is worn. In FIG. 2A, the apparatus isshown unfolded; the substrate is flat, but may be folded (as shown inFIG. 2B) so that the gel pads 207, 209 above and electrically connectedto the electrodes are on the back side of the substrate with the controlcircuitry 211 on the opposite (back) side, and connected by conductivetraces 214, 216. The device may also include one (or more) inputs, e.g.,buttons, dials, etc. FIG. 2B shows the device of FIG. 2A being folded.

As used herein the term “electrode” may refer to both the gel and theelectrical connector and/or any other material forming the interfacebetween the subject and the connection to the control circuitry.

In any of the apparatuses described herein, the conductive gel pad thatconnects electrically to the user's skin to apply neuromodulation may beconfigured within a range of dimensions that may be optimized forneuromodulation. For example, in some variations, the thickness of thegel may be related to the distance of the electrode (e.g., the outersurface of the gel) from the target nerve bundle, when the electrode isworn. This may be equivalent to the distance from the skin surface tothe target nerve bundle. The applied electric field may be optimized tothis gel thickness. For example, if the gel is too thin, the electricfield may stimulate more of the surface nerve to create a discomfort. Ifthe gel is too thick, then the field strength may be less than optimalat the neural bundle that we target.

The skin is not typically homogenous, but includes sweat glands that arevery conductive when wet, and patches of dead skin that are typicallyvery non-conductive. In addition, air bubbles sometimes are trappedbetween the gel and the skin. The air bubbles may cause localconcentration of electric field around them. Occasionally, the gel padmay be partially lifted from the skin due to movements. Further,electric fields may concentrate on the gel pad's boundary that remainsattached to the skin.

In any of the electrodes described herein, a resistive layer may beinserted between the control circuitry output (e.g., the output of thePCBA) and the gel body to evenly distribute the electrical current overthe skin. This resistive layer may stop the current from concentratingon the sweat gland, and may reduce the field concentration around airbubbles and dried skin.

In some applications, the applicants have found that this resistivelayer can be a low cost printed carbon film, or a plastic filmimpregnated with carbon particles. In other applications, a stainlesssteel mesh, which is non-conductive until there is a high enough voltageto break down the surface oxide layers, may be used. The temporarilyhigh-resistance layer (e.g., the property of stainless steel's surfaceoxide) to cause the stainless steel to be non-conductive where there isa high resistance, such as air or dead skin, may protect the areadisrupted by these artifacts. Thus, in some variations a stainless steelmesh may be preferably for both spreading the energy and protecting theuser. In addition, the inherent electrical resistance of very finestainless fibers may also create a resistive layer effect similar tocarbon layers to prevent the local concentration of electrical currentinto sweat glands.

For example, FIG. 3 is a table (based on experimental data) summarizingthe relationship between gel thickness and the distance of the nerve tothe skin. In general for nerve targets that are closer to surface of theskin, a medium thickness gel (e.g., between about 0.5 mm and 1.2 mm) maybe optimal. For longer distances, a thicker gel (e.g., greater than 1mm, greater than 1.2 mm, greater than 1.4 mm, greater than 1.5 mm,greater than 1.7 mm, greater than 1.8 mm, greater than 2 mm, etc.) maybe used.

In addition to the thickness, the location of the electrode gel pad mayalso be optimized. For example, in any of the variations describedherein, the neuromodulator may be positioned behind the user's ear. Inany of the apparatuses described herein that are configured to be placedbehind the ear, an optimal configuration for the neuromodulation (e.g.,electrode) behind the ear for inducing an energizing (e.g., ‘energy’)effect may be having a thickness of, e.g., between about 0.030 inch to0.040 inch (e.g., between about 0.7 mm and 1 mm). Alternatively, in somevariations, the gel thickness optimal for neuromodulation for inducing arelaxed neural effect from behind the user's neck may be between about0.050 inches to about 0.060 inches in thickness (e.g., about betweenabout 1.2 mm and about 1.5 mm). As shown in FIG. 3, thickens of theelectrode (e.g., gel thickness) may depend on the distance to the targetnerve.

The shape of the gel may also be configured and/or adapted (e.g.,optimized) to the application. For example, FIG. 4A shows an example ofan electrode, including a gel pad 407 that may be used behind the earand is configured as an oval; in this example the oval is approximately0.70 inch to 1.0 inch in the major axis, and 0.60 inch to 0.80 inch inthe minor axis. This shape may be optimized to cover the bony protrusionbehind the ear, which is a unique feature and an easy anatomicallandmark for user to recognize for application of the electrode. FIG. 4Billustrates an example of a shape of an electrode (e.g., gel pad) forthe return electrode.

Alternatively, the mastoid (e.g., behind the ear) electrode, includingthe gel, may be wedge shaped, as shown in FIG. 4C. In this example, thewedge-shaped electrode (left) may including a slightly tapered shapethat may conform well to the region behind the user's ear. Thedimensions shown in all of these figures are examples only, and otherdimensions may be used (e.g., +/−10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%,90%, etc.).

In some variations, the apparatus includes an electrode having a gelthat is configured, including shaped, to fit on the back of the neck.For example, in some variations, the electrode is configured to targetthe nerve bundle behind the neck and is configured as a rectangle (e.g.,FIG. 5A or 5B), e.g., with rounded corners 0.9 inch to 1.2 inch inwidth, and 0.8 inch to 1.1 inch in height. In this example, the top edgeof this gel may be placed at the end of the hair line, where the neckhas a natural fold. This anatomical landmark may allow the user totarget the proper nerve bundle.

In any of these apparatuses, the reference electrode may provide areturn path for the neural modulating electrical current. The shape ofthis electrode may affect the field distribution in the area between thetwo electrodes. The apparatuses described herein may be configured tohave a uniform electric field at the target nerve bundle. For example,see FIGS. 4B and 5B. The apparatus may be positioned on the subject sothat the nerve bundle targeted for modulation is positioned between themodulating electrode and the reference electrode. Therefore the distancebetween the two electrodes may be controlled. For example, FIG. 4B isone example of a reference electrode shaped to optimize electric fielduniformity at the target neural bundle.

The applicants have found that it is surprisingly effective if thereference electrode is larger than the neural modulating electrode; thisconfiguration may provide greater comfort of the user, minimizing thetingling sensation from the surface nerve that comes with theneuromodulation. For example, the reference electrode may be betweenabout 110% and 200% the size of the modulating electrode (e.g., theelectrode positioned in these examples, over the mastoid and/or on theneck); compare FIG. 5A (showing the modulating electrode for the neck,which may provide a “calming” neuromodulatory effect when a particularwaveform is applied, as described herein) with FIG. 5B, showing itsreference electrode.

Any of the apparatuses and methods described herein may be configured toform self-contained (e.g., limited-number-of-use) wearableneuromodulators that include printed conductive traces and/or wovenconductive traces between control circuitry and the (e.g., gel)electrodes. The apparatuses described herein may be low-cost, andhigh-reliability. Any of these one-time use devices may achieve very lowcost fabrication by utilizing automation in the assembly of the device;the use of printed layers and traces on a flexible substrate to conductthe neural-modulating waveforms generated at the control circuitry(e.g., printed circuit board) assembly to the skin contacting gelelectrodes.

For example, printed traces may mate to the control circuitry (e.g.,PCBA) via a compression force generated by dimples on the plastichousing forcing the printed traces against contact pads on thecircuitry. For example, FIG. 6A shows one example. In FIG. 6A, theconductive traces consists of nanoparticles of silver that are dispersedin a binding medium, or alternately (and potentially lower cost), carbonparticles may be used instead of silver particles. The traces may belaid down using a silkscreen process or an ink jet printing process. Theink may be formulated for flexibility so that it will not fracture whenthe substrate bends.

In FIG. 6A, the apparatus includes a housing or enclosure 601 that atleast partially encloses the control circuitry 603 and may be connectedto the flexible (e.g., woven) substrate 605. The housing/enclosure inthis example includes two parts that are connected (e.g., snapped, viafriction fit, welding, screw, etc.) so that the substrate 605 andconductive traces (which may be printed or otherwise formed on thesubstrate, or may be separate from the substrate) are held between theparts of the housing/enclosure so that it is both secured to thesubstrate and connected (via one or more connecting pads electricalcommunication with the control circuitry 609. In FIG. 6A, the first(e.g., upper) portion of the housing 601′ includes a detent, dimple,projection, tab, etc. that applies force to maintain a connectionbetween the conductive trace 611 and the circuitry 603. Thus, any ofthese apparatuses may include a compression contact between theconductive traces and the control circuit (e.g., PCBA).

For example, FIGS. 6B-6D illustrate examples of methods for connecting aconnector (e.g., a stainless steel interwoven yarn in this example) tocontrol circuitry. In FIG. 6B a compression lock includes a crimp pin621 that is used to crimp 629 the conductive yarn 623 to an electricalconnector (e.g., solder tab 627) for a control circuit. FIGS. 6C-6D showexamples in which a rivet 632 is used; in FIG. 6D the rivet is an openrivet 632′. In FIG. 6E, the connector may include an upper housing 641and a lower housing 642 that can be locked together to secure theconductive yarn 623 to the conductive pad of the control circuit.

FIG. 7 is another example of a limited-number-of-use neuromodulator thatis configured to be worn behind the user's neck. In FIG. 7, theapparatus has a generally hourglass shape with a first 701 (e.g., upper)electrode (gel electrode) and a second 703 (e.g., lower, or return)electrode. The example shown in FIG. 7 includes exemplary dimensions.The control circuitry 707 in this example is connected to the electrodesby connecting wires 705, 706. The control circuitry may be enclosed in ahousing (e.g., enclosure) as illustrated in FIG. 6A. The apparatus inFIG. 7 is also configured as a limited-number-of-use device and may bepackaged in a sealed pack similar (e.g., limited-number-of-usepackaging). The device is self-contained, and includes a battery (notshown in FIG. 7) and a miniature control circuitry (e.g., PCBA) that maycontain the circuit necessary for neuromodulation. The device may beattached to the user (by the user) behind the neck, with the largerelectrode placed on the shoulder region (e.g., C4-T3, e.g., C5-T1) andthe small electrode on the back of the neck below the hair line (e.g.,C1-C6, e.g. C2-C4).

FIGS. 8A-8F show an example of a self-contained neck-worn apparatus,similar to that shown in FIG. 6, having different layers or region alsoshowing exemplary dimensions. In FIG. 8A the substrate 803 (e.g.,printed substrate) may include two or more contact regions 805, 807,e.g., formed by printed silver, for high conductivity, which may becovered by a 3^(rd) layer of carbon ink at the gel pads for controllingits electrical resistance and distributing electrical current evenly tothe skin even in the presence of inhomogeneous structures. An additionalprinted layer (shown in FIG. 8B), may consist of an electricallyinsulating dielectric 812 so as to keep the traces from exposing to theuser. FIG. 8C shows an example of a pattern of the conductive silverlayer that may be used, while FIG. 8D shows an exemplary pattern of thecarbon layer that may be used. FIG. 8E illustrates an exemplary patternfor the dielectric layer, while FIG. 8F is an example of the oppositeside of the apparatus. In this example two rivets are shown to bring theelectrical connection to the other side of the substrate. Alternatively,a folding technique such as disclosed above may be used to bring theconducting traces to the other side of the apparatus, where the controlcircuitry (e.g., PCBA) resides.

The substrate and traces may be printed repeatedly on a large sheet thencut into individual units for substantial cost reductions, asillustrated in FIG. 9, showing a printed substrate that is repeated manytimes on a large sheet for mass reproduction. Printing many of theseelectrodes on a single sheet may allow them to be cut apart andseparated later, after reliably screening/printing them. As discussedabove, the substrate may be a paper, polymer or in some variations, awoven material (including braided, knitted, etc.), and the electrode 905may be printed for each apparatus 903 in a batch manner.

Any of the apparatuses described herein may use a mesh, such as astainless steel mesh. In particular, a mesh, such as a stainless steelmesh, may be used to spread the current in the electrodes. For example,the Applicants have found that a stainless steel mesh made of very finestainless steel fibers may be an excellent way to distribute current forneuromodulation when used as a current spreading layer placed betweenthe control circuitry output and the electrode (e.g., gel layer) forskin coupling. For example, FIG. 10A illustrates one example of astainless steel yarn 1001 that is interwoven with a polyester yarn 1003.The yarn 1003 in this example is electrically insulative. The stainlesssteel wire mesh may spread the electrical current uniformly throughoutthe gel, while the gel conforms to anatomical contours of the wearer fora better adhesion to the skin. FIG. 10B is a schematic illustration of amesh formed of a non-conductive polymer (e.g., a polyester yarn) andstainless steel wires.

The gel electrode may be held in intimate contact with the user's skin,preventing stimulation of surface neurons that may irritate and/ordistract the user. This intimate contact may be achieved when there isno rigid object around the electrode (such as connection snaps). Becauseof the stainless steel's mechanical properties, there is a memory in themesh layer that may help it stay in a contact shape once pressed againstthe anatomy. The shape retention may help the gel pad to stay in placeand make more intimate contact with the skin. In addition, the s steelis resistive to electrical current flow, so that the mesh, along withthe gel pad, may spread the electrical currently evenly over the surfaceof the skin. The Applicants have found that a woven stainless mesh madeof fine wires, e.g., 40 gauge or finer, inter-woven with anon-conducting fiber such as a polyester yarn may provide a combinationof electrical resistance, retention of shape, and mechanicalflexibility/softness, and the ability to spread the electrical current.

FIG. 11 illustrates another example of a contact including an insulativeyarn combined with stainless steel filament(s). In this example a bundleof stainless steel wires 1101 may be interwoven with a polyester yarn1103. A polyurethane adhesive may be used to hold a stainless steelbundle 1105 in intimate contact with the mesh. Thus, FIG. 11 illustratesone method of forming an electrical contact with a stainless-steelinterwoven weave (fabric), by making electrical contact using a pigtailof stainless steel fine wires adhered to the fabric (e.g., using apolyurethane).

For example, in some variations, a woven, insulating polymer fabric maybe used as substrate, and may include conductive fibers (e.g., stainlesssteel fibers in the yarn interwoven at periodic locations). FIG. 12illustrates an example of a method of manufacturing such apparatuses. InFIG. 12, the stainless steel mesh is interwoven with the fabric yarn inregions 1202 (periodically repeating regions). Thenon-electrode/nonconductive regions may be woven, but may lacking theconductive fibers (e.g., stainless steel fibers). Once or more controlcircuits 1203 may be attached to the woven substrate, either directly(e.g., using an adhesive) or through a housing (as shown in FIG. 6A,above). A gel (e.g., hydrogel) forming a gel pad 1207 as describedherein may be electrically continuous with the regions of the meshincluding the conductive fiber 1201. The electrodes, including the gelpads, may be connected via one or more wires, conductive traces,conducive yarns, etc. 1211 to the control electronics. The connectorsmay be stitched, embroidered or otherwise attached to the wovensubstrate. In some variations, the conductive trace is printed onto thewoven substrate. These apparatuses may be fabricated as sheets(illustrated in FIG. 12) that may be cut apart, as shown in FIG. 12. Anyof these apparatuses may also include a battery, e.g., conned to thecontrol circuitry (including within or adjacent to anyhousing/enclosure).

FIG. 13 illustrates another manufacturing technique, in which astainless steel yarn 1301 is embroidered onto the gel pad area 1305 ofthe substrate to form a current-spreading mesh that is positioned underthe gel pad.

FIG. 14 is another example of a substrate formed by a woven polymericyarn or material 1401 into which fibers of conductive material (shownhere as stainless wires) is woven. In FIG. 14, the polymeric fibers arewoven to form the substrate and specific, conductive regions, e.g.,underlying the electrode regions where the gel pads will be located, isinterwoven with the conductive fibers (e.g., stainless steel fibers).For example, in FIG. 14, the stainless steel wire is, e.g., 100 gauge(e.g., 0.25 mil) wire and the polymer weave is formed of a polyesterfiber (e.g., 0.1 mil). The number of stainless steel wires in the yarnmay be approximately 30 (−30), and the yarn diameter may beapproximately 14 mil. The square grid weave shown has a pattern ofapproximately 40 mil center to center.

FIGS. 15A-15B illustrates an example of a woven substrate includingconductive fibers in a conductive yarn that may be used. FIG. 15A is across-sectional view of the first electrode region of an apparatus,showing a conductive gel having an approximately 30 mil thickness over awoven polyurethane substrate; underlying the conductive gel is aconductive yarn that if formed of a polyester material into which astainless steel wire (e.g., 0.25 mil) is interwoven. FIG. 15B shows anenlarged view of the conductive yarn.

FIG. 16 is another example illustrating the use of the 3D wovensubstrate. In FIG. 16, the substrate is a woven material (e.g.,polyester) to which the circuitry may be attached in a housing 1605enclosing control circuitry (PCBA) 1607. In this example, the electrodesare formed by stainless steel-interwoven yarn 1609 that is stitched,woven or otherwise attached to the substrate and onto which a conductivegel pad 1611 is formed. The electrodes 1603, 1603′ (formed by theconductive gel and underlying stainless steel yarn) may be electricallyconnected to the control circuitry within the housing by a conductorsuch as a stainless polyester yarn 1613, as shown in this example. InFIG. 16, the stainless polyester yarn conductor is attached via anadhesive (e.g., polyurethane glue) 1613.

FIG. 17 schematically illustrates an alternative variation in which thehousing enclosing the control circuit also forms a control (e.g.,button) that may be actuated by the wearer/user. In this example, thehousing 1705 is configured to be pushed to operate a control (e.g.,button) and also supports electrical contacts between the controlcircuitry 1707. The conductive trace/electrical connector 1715 isconnected to the control circuitry by a mechanical securement (shown asa dimple in this example) 1721 that also secures the housing to anextension (e.g., a ‘finger’) of the woven substrate 1701′. In thisexample, the skin-contacting side of the substrate may make a singlepoint of contact with the micro-switch 1731 and the woven substrate1701. The skin-contacting electrodes 1703, 1703′ may be formed asdescribed herein.

FIGS. 18 and 19 illustrate alternative examples in which the housing isalso configured as a button connected to the control circuit. In FIG.18, the button is a micro-switch 1831 that is mounted to the controlcircuit(s) within the housing/enclosure and the housing is sewn orstitched to the substrate (e.g., woven substrate) by a fiber (e.g., yarn1833). In FIG. 19, the mount 1934 for the housing (connecting thehousing to the substrate) may also include one or more conductivecontacts and may make electrical contact between the electrode(s) andthe control circuit(s) within the housing, e.g., via an electricallyconductive yarn 1933.

Any of the apparatuses described herein, with or without a wovensubstrate, may include a cover or wrap (housing) enclosing all or partof the power source and control circuitry; this cover may be formed of adifferent material than the substrate, and in particular may be apolymeric fabric. FIGS. 20 and 21 schematically illustrate alternativeembodiments. In FIG. 20, in addition to the underlying substrate, afabric material 2041 may be positioned over the housing for the controlcircuitry (or just over the control circuity if a housing is notincluded). This may cover and protect tee electronics. Although anyvariation of the attachment of the control circuitry to the substratemay be used, a variation similar to that shown in FIG. 18 is shown inthis example. In FIG. 20 the cover fabric may be a woven material(including the same or a different material as the substrate). Forexample, in FIG. 21, the cover is not a woven material, but may be apolymeric material (e.g., a plastic) such as a plastic bag; thepolymeric cover may be part of the enclosure/housing for the controlcircuitry, as shown. The enclosure may therefore by sewn or otherwiseattached (e.g., adhesively attached) to the woven substrate.

In any of the variations described herein, the conductive yarn, mayinclude a plurality of conductive strands or fibers (e.g., of stainlesssteel). In some variations, these strands may be woven into the mesh orweave of the electrode(s) of the apparatus by forming a pig-tail likeconnection in which the various conductive fibers radiate outward. Insome variations, the conductive fibers may radiate outward from theconductive connector, which may be yarn including the stainless steelfibers that may connect the electrode to the control circuitry. Forexample, FIG. 22 illustrates an example of a woven stainless-steel yarn2202 that is both the connector to the control circuitry (not shown) andthat extends radially outward to form a conductive mesh within theelectrode underneath a conductive gel pad (not shown).

For example, FIG. 23 illustrates another example of a neuromodulatorapparatus that is configured for limited-number-of-use and includes awoven substrate (this example is configured to be worn behind a user'sear, in the mastoid region), in which a stainless steel mesh is used toform part of the electrode(s).

FIG. 24A is another example, showing a different form factor, alsoconfigured to be worn behind the user's ear. In both examples, thecontrol circuitry, battery, control input (e.g., button), electricalconnectors (e.g., conductive traces, wires, woven fibers, etc.) andelectrodes) are all attached to the woven substrate 2401. The substrate2301, 2401 may be folded over to make the connection to the subject.However, in FIG. 24A, the first and second electrodes (anode andcathode) are nearly adjacent to each other, so that the center of eachconductive gel pad of the electrode is only separated by each other byless than about 3 inches (e.g., less than 2 inches, e.g., less than 1.5inches, etc.). In FIG. 24A, the first and second electrodes areseparated from each other (on center) by about 1.25 inches.

Thus, a limited-number-of-use neuromodulator device configured to beworn on user's skin over the mastoid region, may include a flexiblesubstrate 2401 (which may be any flexible materials suitable for printedelectronics such as Polyethylene terephthalate (PET), polyimides,polyurethanes, polyethylene, polypropylene, etc.). The device mayinclude a first electrode 2405 having a tapered profile (e.g.,approximately triangular, also in FIG. 4C, on the left, which may alsobe referred to as ‘wedge-shaped’) on the flexible substrate. This firstelectrode may be at the narrow vertex of the device. As alreadymentioned, the first electrode may include a first conductive gel pad(visible, outward-facing portion). Although the first electrode isapproximately triangular- or wedge-shaped, it has rounded edges; inaddition, the long sides of the profile of the electrode (e.g., the gelpad) may be bent or curved. In FIG. 24A, the bottom of the electrode isrounded. This shape may help distribute current and prevent irritation.

The device shown in FIG. 24A also includes a second electrode 2407 onthe flexible substrate. The second electrode typically includes a secondconductive gel pad. As mentioned, the center of the first conductive gelpad is separated from a center of the second conductive gel pad by lessthan, e.g., two inches. The second electrode (e.g., the gel pad) mayhave a different shape than the first electrode (e.g., round, rounded,oval, etc.).

The exemplary device shown in FIG. 24A also includes a control circuit2409 mounted on the flexible substrate and a power source 2411 inelectrical communication with the control circuit on the flexiblesubstrate. In general, the control circuit is configured to deliver aconstant-current waveform between the first and second electrodes. Thecontrol circuit may include hardware, software of firmware that isconfigured (e.g., pre-programed, hardwired, etc.) to deliver an “energy”waveform that is designed to evoke a feeling of energy in the userreceiving the waveform from the device, when worn behind the ear.

The substrate in FIG. 24A may be any appropriate flexible substrate,including (but not limited to) fibrous, e.g., woven, substrates. In FIG.24A, most or all of the elements (e.g., electrodes, control circuit,battery, electrical connection (shown as electrical traces 2415, 2416)are on a first side of the substrate, and the substrate is folded backon itself, so that the electrodes face the user (when worn) and thecontrol circuitry and power source face away from the subject. Theconnectors (e.g., electrical traces) extend along the first side, overthe hinge region 2432, and along the second side to the circuitry. FIG.24B shows the user-contacting side of the folded-over device. The devicemay be fixed (e.g., adhesively, stitched, welded, etc.) in this foldedover configuration.

Although FIG. 24A-24B shows a specific embodiment, any of the featuresshown herein may be used or adapted into any of the other embodimentsdescribed herein, and similarly, any of the alternative featuresdescribed herein may be included as part of a variations such as shownin FIGS. 24A-24B. For example, the control circuit(s) may be housed in ahousing (or enclosure) enclosing the control circuit and coupling thecontrol circuit to the substrate.

As mentioned, any appropriate substrate 2401 may be used, including afibrous substrate (e.g., a woven substrate). For example, the substratemay be a woven insulating material.

In some variations, the apparatus may include a control input 2409 thatis electrically coupled to the control circuit and configured to controlone or more of: power (e.g., on/off and/or pause/resume) and intensity(e.g., amplitude of the applied voltage) of the device. Alternatively,in any of these variations the apparatus may not include a controlinput, and may instead autonomously function without any control input.Thus, in some variations the control circuitry may automatically apply awaveform after power is applied to the control circuitry, e.g., uponremoval from the packaging and withdrawal of any circuit interrupt. Insome variations the apparatus may determine that or when the electrodesare in contact with skin, e.g., based on impedance between theelectrodes, and may automatically apply the waveform only when skincontact is confirmed.

As shown in FIGS. 24A and 24B, the outer surface area of the secondelectrode may be larger than an outer surface area of the firstelectrode.

Any of the devices described herein may include a first plurality ofconductive filaments attached to the woven substrate. The plurality ofconductive filaments may be configured to distribute current within thefirst conductive gel pad. The plurality of conductive filaments may bestainless steel filaments having a diameter, e.g., of 40 gauge or finer.

In FIG. 24A-24B, as in any of these examples, the thickness of theconductive gel pads may be configured to optimize treatment (see, e.g.,FIG. 3, above). For example, the first conductive gel pad and the secondconductive gel pad may each have a thickness of between about 0.030 inchto 0.040 inch in FIG. 24A; this thickness may be specific to the use ofthe device for stimulation behind the user's ear (e.g., over the mastoidregion).

In FIG. 24A, the substrate configured to be folded over itself so thatthe first and second electrodes are on a first side and the controlcircuit is on a second side, as shown in FIG. 24B. Thus, the finalprofile of the fully-assembled device is a tapered, e.g., wedge-shapedprofile, as shown. This shape may fit well behind the user's ear, overthe mastoid.

Any of these device may also include one or more connectors, e.g., afirst connector electrically coupling the first electrode to the controlcircuit and a second connector electrically coupling the secondelectrode to the control circuit. The connector may be any appropriateelectrical connector (e.g., a conductive yarn, a wire, a printedelectrical trace, etc.). In FIG. 24A-24B the connector is an electricaltrace that is printed or otherwise adhered to the substrate. The firstand second conductor are shown each extending along a first side of thedevice, over an edge of the device (at the fold region 2432) and along asecond side of the device to connect to the control circuit.

The control circuity in any of these devices, including the variationshown in FIGS. 24A-24B, may be configured to provide a waveform that hasa therapeutic and/or neuromodulator effect. For example, the controlcircuit may be configured to provide an amplitude-modulated carrierwaveform having a trapezoidal envelope, wherein the carrier waveformcomprises a pair of repeating pulses. In FIG. 24, the waveform may beadapted to provide an “energy” waveform (e.g., to induce an energizedmental state) similar to the waveform parameters shown in FIG. 30A anddescribed in detail below.

In FIGS. 24A-24B, as in any of the apparatuses described herein, thecontrol circuitry and power source (e.g., battery) may be adapted to bea limited-number-of-use device, having a very high electrical efficiency(e.g., greater than 75% efficient, greater than 80% efficient, greaterthan 85% efficient, greater than 90% efficient, etc.) when convertingthe energy from the power source into electrical output delivered to theuser through the conductive gel pads.

For example, in FIG. 24A (or any of the apparatuses described herein),the power source may comprise a battery having less than a 50 milliamphour capacity (e.g., may be one or more alkaline batteries in serieshaving an instantaneous current output of less than 20 milliamps), and amaximum voltage output for the device is between 10 V and 30 V, yet mayprovide electrical stimulation to the user for more than 15 minutes(more than 20 minutes, more than 25 minutes, etc.) before being removedand recycled/destroyed.

For example, a limited-number-of-use neuromodulator device, similar tothe one shown in FIGS. 24A-24B, may be configured to be worn on user'sskin over the mastoid region and may include: a flexible substratehaving a fabric cover in which the control circuitry and battery areheld between the substrate and the cover; a first electrode on theflexible substrate on the first side, the first electrode comprising afirst conductive gel pad; a second electrode on the flexible substrateon the second side, the second electrode comprising a second conductivegel pad, wherein a center of the first conductive gel pad is separatedfrom a center of the second conductive gel pad by less than 1.5 inches.The electrodes may be concentrically arranged as described below. Thecontrol circuit may be retained above the flexible substrate on thesecond side of the substrate without being attached to the substrate, sothat it may move slightly as the apparatus is flexed. Similarly, thepower source in communication with the control circuit may be positionedabove the flexible substrate. The control circuit is configured todeliver a constant-current waveform between the first and secondelectrodes.

In general, the substrate, including in some variations a fibrous (e.g.,woven) substrate, may allow the device to resume a preset shape even ifdeformed (e.g., during handling, manufacture and/or packaging). Forexample, a three-dimensional (3D) woven stainless yarn may help form theelectrode and may provide a spring force for the skin contact and mayhelp the electrode conform better around areas having a bony structureunder the skin. This may also aid in the ability of the apparatus tobounce back into functional shape after removing from a small packaging.FIGS. 25A-25B illustrate an example of an apparatus having a paper orpolymeric substrate that is not woven, showing bending/deformation ofthe substrate. In this example, the substrate is a fibrous papermaterial (e.g., polyethylene terephthalate, PET) formed of filamentswith a soft filler between the fibers. This material (commerciallyreferred to as Tyvek) may be used in addition to or instead of the wovensubstrates described herein, and may include many of the shape-memoryproperties of the woven materials. For example, in FIG. 25A, theapparatus formed of the fibrous paper substrate is shown able to returnto the original shape after being squeezed into a small package.

Waveforms

In general, the neuromodulation apparatuses described herein maytypically generate high voltage (e.g., approximately 50 volts), constantcurrent (e.g., of up to 25 milliamp) electrical pulses at between 100and 16.0 KHz frequency. In general the charge per phase of the waveformmay be between about 0.1 to 10 μC per phase The circuit must may have ahighly efficient to minimize the size of the battery, and may beextremely low-cost to manufacture, and in particular, may consist of asmall number of components to keep the product light in weight andsmall. Delivering a constant current is desirable given the variabilityin skin and tissue properties between individuals and between two usecases for the same individual. However, constant voltage circuits withvariable current can also be used in part of the waveform.

These requirements may be achieved by the use of a highly efficientcircuit that utilizes knowledge of the skin's equivalent electricalcircuit and the relationship between the constant current electricalpulses and the output voltage. FIG. 26 illustrates one example of therelationship between current 2601 and voltage 2603 during the on time ofthe pulse. A traditional waveform generator with constant currentcapability may use a step-up power supply to bring the supply voltagefrom the battery level (e.g., typically 3 volts) up to the 50 voltsapplied by using a step-up converter; it may then create aconstant-current source from the high voltage power supply, and then putin a switching circuit to generate the pulses. The disadvantage of thetraditional design is that circuit is complex and expensive, and ittakes up a lot of room. The traditional design also keeps the highvoltage all the time, even when it is not needed. The power efficiencyis therefore relatively poor.

Described herein are control circuitry for applying neuromodulation(neuro-stimulation) waveforms, which may be referred to as ensemblewaveforms because they may apply a set of electrical parameters betweenthe electrodes of any of the devices described herein that arespecifically configured to result in a neuromodulator effect and/ortherapeutic effect desired. For example, in some variations the ensemblewaveform(s) to be applied is/are programmed or encoded into the controlcircuitry as software, firmware and/or hardware. The ensemblewaveform(s) may be configured to induce a cognitive effect in thesubject, such as an energizing effect, a calming response, animprovement in memory, etc. In some variations, the ensemble waveform(s)may be configured to induce an energizing response in the user.

The control circuit(s) described here may be configured to provide awaveform having a constant current pulse. Given the electrical model ofthe skin at a particular frequency, this constant current pulse maytranslate into a voltage ramp of a specific shape. This transformationmay map from current pulse to voltage ramp and may be computed off-line,and then stored in the low cost micro-controller chip in thelimited-number-of-use device.

This information may then be used in a pulse width modulation boostconverter (or alternately a pulse frequency boost converter) in whichshort bursts of energy are fed into a small inductor. The inductor mayprovide a high voltage burst with the same energy as the input energypulse.

In addition, the waveform may also be transformed off line to convert adesired voltage ramp into a sequence of input pulses of variousdurations for the kick-up inductor. This mapped sequence of pulseduration may then be stored in the low cost microcontroller, and thenapplied to the inductor through a low cost switching transistor, so thatthe inductor will “kick up” the voltage to achieve a specific ramppattern as desired.

A combination of inductor and capacitor may be used to smooth out thevoltage at the output to get rid of the spikes coming from the pulsenature of the kick-up pulses.

The apparatuses may also include feedback control of the current pulseoutput. For example, due to the variable electrode contact resistance,or the skin impedance reacting to modulation and changing over timeduring a neuromodulation session, the neural modulating current mayfluctuate. This fluctuation is undesirable. An electrical currentsensor, measuring the voltage drop on a resistor connected in serieswith the output, may provide a monitor of the electrical current for avery low cost. This same resistor, along with voltage measurement of theoutput, using Analog to Digital converters built into themicro-controller, may also allow the monitoring of the impedance seen bythe electrode pads.

Any of these apparatuses may also be configured for detection that theelectrode pads are on skin, and ready for applying neuromodulation. Forexample, when the impedance is low, indicating the gel pads are on theuser, the apparatus may detect this and may be configured to allow theneuromodulation to start. To probe the impedance across the electrodepads, a small pulse output may be generated by the microcontroller toapply to the electrodes for this purpose.

FIG. 27 is a circuitry schematic for one example of alimited-number-of-use apparatus as described herein. In FIG. 27, theapparatus is configured for automatic regulation of electrical current.The electrical current sensor in this example feeds back into amicrocontroller so that when the current goes down, the controller putsout more energy into the kick-up inductor so that the output stimulationincreases to compensate for the decreased current.

In any of these apparatuses, the switching transistor may be controlledby the microcontroller to generate kick-up pulses. For example in FIG.27, a Q1 transistor may run a pulse width modulated waveform at a pulserate of about 1,000,000 Hz (1 MHz). The pulse width may range from 200nano-seconds to 900 nano-seconds. This pulse may be applied to aminiature L1 inductor. The size of the inductor is inverselyproportional to the frequency of the pulses. The 1 MHz frequency assuresthat we can use a tiny inductor to keep product small and light weight.When Q1 turns off after a pulse, energy in inductor L1 releases thru D1.This pulse is directed to the skin through P10 (the anode). The currentfrom the skin returns through P11 (cathode) goes thru R9 to return toL1. Note that Q2 and Q5 amplifies the micro-controller's output to alarge enough current to drive the switching transistor Q1.

The apparatuses described herein may provide step up boost converterfiltering. The output of the kick-up inductor may have ripples since thecircuit uses short bursts of energy put into inductor L1 to kick up thevoltage. The apparatuses described herein may include a special designin this filtering to preserve energy and increase efficiency. Forexample, after rectifier D2, the components L2, C2, R4, along with thecapacitance on the skin, may perform filtering of the ripple. Whenfilter inductor L2 is sinking current (taking in current), voltage isgoing down in C1. If the voltage in C1 goes negative, it may take awayenergy. Instead, D6 is connected to reference node (C1's pin away fromL1), so that L2 can take energy straight from the reference node,instead of drawing it from C1 when C1 holds negative charge.

FIG. 28 illustrates simulation results showing the voltage ramp requiredof the boost converter. Note that the shape of the ramp is differentdepending on the duration of the constant current pulse, but is the samefor different current levels. Horizontal axis is time, vertical axis isvoltage at output of boost converter.

In any of the variations described herein, a low cost battery that haslimited instantaneous current capability may be used. For example, aplurality of (e.g., four or more, five or more, etc.) capacitors, suchas C4, C7, C8, C14, C15, may be arranged in parallel to store the chargefrom a low instantaneous current battery such as from an alkaline cell.These capacitors can be replaced by a super-capacitor which will have aneven higher capacitance, though at a higher cost.

Any of these apparatuses may include a skin discharge circuit. Forexample, neuromodulation may include a discharge of the electric chargecumulated on the skin after each neural-modulating pulse. In oneexample, Q4, with a control line from the micro-controller, performs theskin discharge function when it is turned on. Further, any of theseapparatuses may include a safety protection circuit. Although thebattery may hold a very small amount of energy, and therefore theapparatus may be inherently safe due to the limited energy available, itis important that the circuit does not over deliver the current orvoltage to the user. A zener diode D3 (e.g., a diode that conducts atthe pre-set voltage limit) may be used to shunt the energy away from theuser when the output exceeds a pre-determined voltage threshold, e.g.,of 36 volts. When the tripping protection happens, in some variations Q3and Q11 may latch, and may send the fault signal to Q8 which performsshutdown of Q9, and the battery is cutoff from the device for a totalprotection of the user.

Any of these apparatuses may also include neural-modulating currentsensing. For example, the sensing circuit (e.g., the microcontroller)may be configured not to disrupt the sensor so as to maintain accuracy.For example, when the neural-modulating current goes thru P11 to R9, apositive voltage may be developed on C11. Q6 and Q7 both conduct(current mirroring). The voltage drop across R9 may be copied onto R1.The signal may then be acquired by the micro-controller, and used todetermine if the current needs to be boosted or attenuated to maintain astable current, and/or if the pads are attached to the skin and/or ifthe pads came off the skin and the user should be made aware.

As mentioned, any of the apparatuses described herein may be configuredto deliver a waveform having therapeutic effects, including inducing acalming effect. The calming effect may be induced using a waveformcomprising a bi-polar pulse, e.g., a pulse of +ve and −ve current atdifferent times of the modulation. FIG. 29 illustrates schematics forone example of a control circuitry that may provide a calming waveform.In FIG. 29, the schematics illustrate a circuit essentially similar tothat of FIG. 27, described above for generating a constant currentpulse, but also includes a set of 4 transistors to switch the polarityof the neural modulating pulse so that both positive and negative pulsesare available for the modulation. In this apparatus, the transistorswitches are controlled by the micro-controller so that polarities canbe swapped at specific moments during the waveform.

For example, the variations shown in FIG. 29 includes a bridge circuitfor reversal of output polarity under microcontroller control. In thisexample, Q12 is the switch for the positive side of the current pulse,with Q13 forming a current source driver to Q12. When Q12 turns on, thelower electrode receives a +ve voltage (it becomes the anode). Q17 turnson at the same time, connecting the upper electrode to −ve voltage. Theoutput is called the B pulse. When the apparatus is ready to switchpolarity, Q16 is the switch for the negative side of the current pulse.It controls the lower rail of the neural modulating current pulse. WhenQ16 is turned on, it connects the lower rail of the supply to the lowerelectrode. Q14 connects the upper electrode to the +ve voltage. This iscalled the A pulse.

In summary, the A pulse (+ve current pulse from device) occurs when Q16and Q14 turn on; the B pulse (−ve current pulse from device) occurs whenQ12 and Q17 turn on.

In any of these apparatuses efficient and low cost storage of thechanging waveforms for neuromodulation in the limited-number-of-usedevice may be achieved by including a microcontroller and sufficientmemory. For example, a micro-controller having 32 Kbyte of Flash memorymay be used. 16 KB may be used for the main program and the remainingmemory may be used for the storage of the modulating waveform. Althoughin some variations the neural modulating waveform may be fairly complex,a time-segment approach to represent the carrier waveform, needing only4 parameters to fully characterize & represent the base carrier waveformat any one time, may be used.

For example, the carrier waveform may be amplitude modulated to achievethe best effects for neuromodulation, which may allow the storage ofmore than 800 (53×16) waveform transitions. The amplitude modulatingenvelope for the neuromodulation may be a trapezoid, so that through anadjustment of the trapezoid description, the modulation can be a) atriangular pattern, b) a ramping up saw tooth modulation, c) a decayingsaw tooth modulation, or d) a symmetrical or e) a non-symmetrical rampup and ramp down, f) the trapezoid modulation to start with a minimumamplitude that the neurons can respond to.

For example, a complex waveform may be economically described by 13numbers: pulse A length; gap A length; pulse B length; gap B length;pulse A to start with this minimum amplitude, before ramping up; pulse Bto start with this minimum amplitude, before ramping up; duration ofthis minimum amplitude. FIG. 30A is a table illustrating examples ofsome of these descriptors. For example, the duration that the trapezoidwill be ramping up is shown in FIG. 30. FIG. 30A shows 13 storedparameters that may characterize an amplitude modulated waveform. InFIG. 30A, the list includes: pulse A to end with this maximum amplitude,before ramping down; pulse B to end with this maximum amplitude, beforeramping down; the duration of this maximum amplitude; the duration oframping down; the duration in the cycle where there is no amplitudemodulation.

In general, the apparatuses described herein may compriselimited-number-of-use neuromodulator apparatuses configured to be wornon the user's skin for neuromodulation (e.g., to create an energizing orcalming effect, a cognitive effect, such as improved memory, or atherapeutic purpose). These apparatuses (e.g., devices, systems, etc.)may include control circuitry and may include, e.g., printed layeredstructure that can be die cut or laser cut to form the device. Theseapparatuses may include a pair (or more) of electrodes that include aprinted layered structure consisting of at least one layer of aconductive film (such as carbon or silver). Alternately the conductivefilm can be replaced by a stainless steel mesh. The printed layeredstructure may consist of a flexible substrate made of polymer fibers,such as, for example, Tyvek (Polyethylene fiber paper), polyimides,polyurethanes, etc. . . . Alternately or additionally, the flexiblesubstrate can be a woven material (e.g., woven of synthetic fibers), andin some variations may be a knitted material.

Any of these apparatuses may include a printed circuit board assemblyand a power source attached to the layered structure; the controlcircuitry may be formed by the printed circuit board. The printedcircuit assembly may be capable of providing a constant electricalcurrent pulse.

The conductive gel pad may be electrically connected to the controllercircuit(s) (e.g., PCBA) through a conductive film and/or the stainlesssteel mesh. In some variations, the stainless steel mesh layer may bewoven into the substrate in a way that maintains electrical isolationbetween two adjacent pads in the weave. The stainless steel mesh layermay be embroidered onto the flexible substrate in a pattern according tothe anatomy of the target area. For example an oval inner electrode anda concentric reference electrode surrounding the stimulating electrode.

In some variations, a conductive trace from the control circuitry (e.g.,a printed circuit board assembly) to the neuromodulation pads (e.g.,electrode's gel pads) may pass through a 300 to 360 degree bend so thatelectrical connection is brought from one side of the flexible substrateto the other side. The printed circuit board assembly may be housed in ahousing (e.g., enclosure) such as a plastic enclosure with connectors(e.g., mechanical connectors, such as dimples molded into the enclosureso that when a printed trace is inserted into the enclosure, the dimplepresses on the trace to push onto the printed circuit assembly to makeelectrical contact). The substrate may be configured to includeconductive fibers (e.g., made of a plastic polymer, or stainless steel)that may help the disposable device to retain its shape against ananatomical feature that's not flat.

In some variations, the control circuitry may include a wireless, e.g.,radio frequency, emitter that identifies uniquely the device to a backend computer through the internet so that when the device is activated,the user is charged for the service. Any appropriate wireless emittercan be a near field communication device (NFC), or a blue tooth device,or a Wi-Fi radio working in conjunction with a phone or a wrist watch ora router. Alternatively, in some variations the simplified device maynot provide output or receive input.

The control circuit(s) (e.g., control circuity assembly) may contain aswitching device (a transistor for example) switching on and off in apattern that generates a DC voltage that changes amplitude with time sothat the current going through the user's skin is a constant currentpulse. The control circuity may contain an energy storage device thatstores the energy from a battery with limited current output capabilityso that there is sufficient energy to generate a neural-modulatingconstant current pulse before going back to a rest state to cumulateenergy for the next pulse.

Any of these apparatuses may include a substrate that is woven orfibrous so that the substrate will unfold once removed from a miniaturepackaging and ready for neuromodulation. If fibrous, the fibers can bepolymer strands, stainless steel strands, carbon fiber strands, or glassfiber strands. In some variations, the substrate may be a wovenmaterial. The fibers may allow the user to squeeze the device into aball or other compact shapes for storage after use or between uses. Thedevice will bounce back in shape once taken out of the container.

In any of the apparatuses described herein, the electrode may include agel pad; the gel pad may contain an FDA approved chemical for cutaneoususe to enhance the electrical conductivity of the skin where the gel isin contact. For example, the chemical may include a fragrance or a legalstimulant that embarks a sense of energy for the user. For example mildCapsicin or Menthol. The gel pad may be a cotton pad infused withphysiological saline or other solutes that goes into the skin throughthe electrical current applied with the purpose of assistingneuromodulation.

In any of these variations, the substrate may include “bumps” atlocations where the substrate folds. The bumps may protect theprinted-on conducting traces to limit the bending angle of the fold toavoid trace damages at the fold.

In any of the apparatuses described herein, the apparatus may include abattery. The battery may have less than about 80 milli-Amp hours incapacity due to the high efficiency of the circuit. For example, thebattery may be a lithium polymer battery or 2 lithium polymer batteriesin series with instantaneous current output capability less than 20milliamps.

In any of these apparatuses, the control circuitry may have 10 or lesscomponents in the constant current pulse generating circuit. The controlcircuitry may be a printed circuit assembly (PCBA) that is about 1 cm×1cm in size (or smaller). The maximum voltage output of the device may bebetween 10 volts and 50 volts (e.g., 20 V, 30V, 35V, 40V, 45V, etc.).The pulses going to the boost inductor in the control circuitry may beshorter than 1 microsecond in duration. These pulses may increase induration monotonically during the delivery of a constant current pulse.A single resistor may be connected in series to the output of theapparatus and may measure the neuromodulation current.

In any of these apparatuses, the electrode may include an Ag/AgCl layer.The thickness of the Ag/AgCl layer may be dependent upon the maximumdosage to be applied by the apparatus. In some variations, a change incolor when Ag is exhausted may provide a feedback to the user that thedose was delivered correctly. The thickness of plated silver may be lessthan 100 micron.

As mentioned, in some variations the substrates described herein may beflexible substrates, including woven substrates. In addition, theflexible substrate may be fibrous (e.g., plastics, paper, etc.). Forexample, a moldable pulp may be used to form a 3D shape to cover theelectronics. Silver ink may be printed on paper to facilitate drying andincrease conductivity by spreading silver ink into paper. Folding thesubstrate before a silver ink is fully hard may avoid cracking of atrace. Printing of an insulator may limit folding radius to preventcracking of traces during fold. Any of these apparatus may use a fibrousmaterial such as polyethylene fibers (e.g., Tyvek) as the substratewhich may have a flexible material that bounce back in shape.

In general, the apparatus may be extremely lightweight. For example, theapparatus may have an overall weight of less than 1 oz., <15 g, <10 g,etc. The overall weight may be <7 grams (e.g., battery 1 gram, PCBA 2grams, substrate/paper 1 grams, gel 3 gram) for a fully enclosedapparatus, which do not require a reusable connector between the gel padand the control circuitry.

Any of the electrodes described herein may include a gel pad; the gelpad may be reasonably thin, but may use a material such as a mesh ofconductive fibers for resistance spreading of the current evenly throughthe electrodes. This may be provided by, e.g., thin carbon traces. Forexample, isolated islands of gel may contact carbon pads. Alternativelyor additionally, carbon

Any of the apparatuses described herein may include a no controls (e.g.,no buttons, etc.) and no control interface. The apparatus may include anauto-off after some amount of time (e.g., 10 seconds, 20 seconds, 30seconds, etc.) of inaction when device is off skin.

The control circuitry for any of the apparatuses described herein may beconfigured to include a self-contained pulse generator; this pulsegenerator may use up to n transistors (where n is 3, 2 or 1) to generatethe high voltage constant current pulses. The control circuitry mayinclude a single transistor for discharge. The control circuitry mayinclude polarity reversal (for bi-phasic waveforms), and may use up to 6transistors.

The apparatuses described herein may include one or more integratedfeatures. For example, any of these apparatuses may include a silvertrace, carbon ink to spread out current, silver on cathode to replenishdepleted Ag+ ion, and a gel pad. Any of these apparatuses may also oradditionally include one or more integrated on-skin detection andpads-off detection.

In general, the waveforms described herein may be used may be of anyappropriate complexity including, e.g., 3 or more segments, 2 or moresegments, etc.). For example 4 or more segments for biphasic waveformsmay be used. The duration of (uninterrupted) stimulation by thelimited-number-of-use device may be any appropriate duration. Forexample, the duration may be a stimulation length of, e.g., <15 minutes,<10 minutes, <5 minutes, <3 minutes, etc. In general the duration may 15minutes or less (less than 25 minutes, less than 20 minutes, less than17 minutes, less than 15 minutes, less than 10 minutes, between 1 minuteand 25 minutes, between 1 min and 20 minutes, between 1 minute and 15minutes, between 3 minutes and 15 minutes, etc.)

Any of the methods (including user interfaces) described herein may beimplemented as software, hardware or firmware, and may be described as anon-transitory computer-readable storage medium storing a set ofinstructions capable of being executed by a processor (e.g., computer,tablet, smartphone, etc.), that when executed by the processor causesthe processor to control perform any of the steps, including but notlimited to: displaying, communicating with the user, analyzing,modifying parameters (including timing, frequency, intensity, etc.),determining, alerting, or the like.

Waveform Charge Per Phase

As mentioned above, in general, the methods and apparatuses describedherein may be configured to provide a change per phase, Q (μC perphase), where Q may be defined as:

Q=(1000/F)*(C)*(pDut)*(pDC)

where F is Frequency, C is current (mA), pDut is duty cycle percentage,and pDC is the DC percentage. Examples of waveforms sown to be effectiveand their corresponding values for Q, F, C, pDut an dpDC are shown inFIG. 30B (Table 3).

Examples of the energy patch (energizing) waveforms that may be used arein rows 8-14 (Base 450 Hz to Base 1500 Hz). These may be applied in aconcentric electrode format (see FIGS. 33B and 34A-34C, below) behindthe ear within the examples described herein. The applied frequencyregime may lead to different sensations for the user; the energy regimeis approximately the same across these waveforms with between about 0.5and 2 μC per phase (e.g., 0.5-3 μC/phase). In general, the waveformsherein may be between about 0.1 to 10 μC per phase. FIG. 30B also showsexamples of waveforms that may be used to treat a disorder (such aspsoriasis) as well as waveforms that may be used to evoke a relaxedcognitive state.

Pendulum Waveforms

Any of the waveforms herein may be pendulum waveforms. A pendulumwaveform ‘swings’ back and forth around a center frequency or centeramplitude or center duty cycle. For example, in some variations thefrequency may be shifted (either continuously or as a step function)over a range of frequencies; the shifts do not need to be symmetriceither in their time or their extent. For example, a pendulum cycle maytake 2 to 20 seconds (e.g., between 5-11 second, about 8 seconds, etc.)for the full cycle. Two examples are described herein: (1) See FIG. 48(“extra strength” strong sensations) and (2) see FIG. 49 (milder,smoother).

Pendulum waveforms may allow the waveforms to evoke a more reliableresponse from the subject because, e.g., changing parameters in thistime scale may prevent adaptation. In addition, sweeping over a rangemay allow more users to experience an optimum spot in terms of sensationand effect, even given people vary anatomically and biologically in thatparticular region with respect to nerve anatomy/physiology and sensoryresponses.

Simplified Neuromodulator

FIGS. 31A-31F illustrate one example of a first variation of aneuromodulator apparatus 3100. In this first example, the device issubstantially flat, and includes a flexible substrate 3103 to which apair of electrodes is attached. The first electrode includes a printedelectrical contact in electrical communication with a conductive gel(e.g., hydrogel) that is sufficiently adhesive to hold the apparatusonto the skin until peeled off. An inner electrode 3107 also includes anelectrical conductor in communication with a hydrogel. The innerelectrode may be concentrically surrounded (completely surrounded, asshown in the example of FIGS. 31A-31H, or partially surrounded, asdescribed below. In FIGS. 31A-31D, the opposite side of the substrateinclude a fabric cover 3111 that may be adhesively secure to thesubstrate and may be wrapped around and/or at least partially enclosethe control circuity and power source (within 3109). Thus the top of theexemplary device shown in FIGS. 31A-31H is an elastomeric fabricmaterial, which may include an elastomeric cotton, for example, anelastomeric nylon, etc. FIGS. 31E-31H show side and front/back views ofthe apparatus of FIGS. 31A-31D. The elastomeric fabric cover material3111 may be secured over the top of the substrate 3105 and the hydrogelelectrodes 3105 may be attached to the bottom of the substrate, as shownin FIG. 31E. In this example the battery and the circuitry are enclosedwithin a housing formed by the elastomeric fabric; a frame or internalhousing may hold the battery and control circuitry and may be wrappedwith the elastomeric material.

In FIG. 31A-31H, the neuromodulator apparatus configuration may have apolyurethane substrate with silver forming the electrodes and traces.Axelgaard hydrogel may be applied to the electrodes in a concentricpattern, as shown. A liner may protect the hydrogel until the apparatusis to be used and applied. On top of the substrate, a battery, PCBA anda top cover made from elastomeric cotton with an acrylic adhesive on theunderside may be used. An optional foam layer may be included.

The apparatus of FIG. 31A may also include a circuit interrupt, such asa pull-tab that may be removed to connect the battery to the controlcircuitry (not shown in FIGS. 31A-31H). Another example, showing a pulltab (circuity interrupt) 3208 is included as shown in FIGS. 32A-32H. InFIG. 32A the apparatus 3200 also includes a fabric (e.g., an elastomericfabric) material cover 3211, wrapping an enclosing 3209 the power sourceand control circuity (not visible). A pair of concentric electrodes(including concentric hydrogel regions 3205, 3207) are attached on theflexible substrate 3203. However in this example, as shown in FIGS.32E-32H, a second hydrogel layer 3221, separated from the first hydrogellayer 3207 by a release layer 3225, may be included. Thus, any of thesedevice may be configured two or more uses.

In general, these devices may include a circuit interrupt, such as apull tab 3208, that is removed to engage the battery and start thestimulation. The device typically will not apply energy to the controlcircuitry the circuit interrupt is removed. Once remove, the apparatuswill not apply a waveform until it detects that the electrodes are incontact with skin (e.g., via electrical measurement, e.g., impedance,resistance, etc.).

FIGS. 33A-33B illustrate top and bottom views, respectively, of aprototype apparatus for delivering neurostimulating waveforms asdescribed herein. In FIG. 33A, the top of the device is covered in anelastomeric cotton material that wraps around and encloses the controlcircuitry and battery. The bottom shows the concentric electrodes (firstelectrode 3305 and second electrode 3307). This device is light (<15 g)and very flexible.

FIG. 34A shows an exploded view of another variation of an apparatus,similar to that shown in FIG. 32A-32H. The apparatus includes a thin andflexible substrate (e.g., urethane 3419, onto which the electrodes 3416,3418 and a connector trace 3420 have been printed. A pair of hydrogelregions, including a first hydrogel layer 3421 and a second hydrogellayer 3425 are layered onto the substrate on the bottom; the first andsecond hydrogel layers are separated by a release layer 3423. Therelease layer in this example is formed of an electrically insulatingmaterial that allows electrical connection between the hydrogel regionsbecause of the cut-out openings over these regions, as shown. Theelectrodes are connected via the flexible traces (formed of thesubstrate) 3420 to the control circuitry 3413. A pull tab 3417 isinterposed between the control circuitry and the battery 3411 (a sleeve3415 for the pull tab may be included to allow it to slide freely out ofthe device when pulled). In this example, a frame 3405 and spacers 3407,3409 may be included to hold the battery and circuitry, though theframe, battery and circuitry may be held between the cover 3401 and thesubstrate without being glued or attached onto the substrate. One ormore separators 3403 may be used. FIGS. 34B and 34D show additionalexploded views. For example, FIG. 34C shows the removable ‘first time’or outer gel layer; the release layer may be pulled (by pulling therelease layer pull tab 3414) to remove the outer hydrogel layer(s) 3425,exposing he inner layers. One or more components shown in the explodedviews of FIGS. 34A-34C may be omitted from some of the variationsdescribed herein. For example, the device may not include a releaseliner and second hydrogel, a sleeve for the pull tab, a spacer, a frame,etc.

In FIG. 34B, the frame sub-assembly (e.g., frame 3405, spacers, etc.),battery 3411 and control circuity 3413 are shown removed from the fabriccover 3401. The flexible traces may connect the first 3416 and second3418 electrodes on the substrate to the control circuity.

FIG. 34C shows the first hydrogel layer 3425 that includes a firsthydrogel that forms part of the first (concentrically arranged, outer)electrode and a second hydrogel that forms part of the second (inner)electrode. A second hydrogel layer 3421 may include a third hydrogelthat overlies the first hydrogel and is in electrical contact throughthe release layer 3423, which includes openings (e.g., cut-out regions)as shown. Similarly, a fourth hydrogel may overlay the second hydrogelof the second (inner) electrode and may also connect electricallythrough the release layer. In this example the release layer is formedof a fluorinated ethylene propylene (FED) film that has holes formed init for electrical conductivity. The release layer also includes a tab(release layer pull tab) that can be used to peel away the release layerto remove the first (outer) hydrogel layer.

FIGS. 35A-35B illustrate one example of a method of wrapping anelastomeric fabric cover over the battery and/or circuitry. In thisexample, the fabric material may include an adhesive on one side (e.g.,an acrylic adhesive) that can be used to wrap and secure the batteryand/or control circuitry (and in some variations, a frame holding one orboth of these). The fabric cover may also be attached (e.g., adhesively)to the back side of the substrate. In FIG. 35A the cover material(adhesive elastomeric material) 3501 is cut into a shape that allows itto wrap around the battery, frame, etc., as shown in FIG. 35B.

FIG. 36 shows another example of a neuromodulator apparatus in which thecover (e.g., in some variations a fabric cover) is removed. In thisexample, the battery 3607, and control circuitry 3605 are exposed, above(but not attached onto) the substrate on which the electrodes are formed(not visible in FIG. 36). In FIG. 36 a first circuit interrupt (pull tab3615) is inserted under a clip 3631, preventing electrical connectionbetween the battery and the control circuitry. A second clip 3617 mayhold a second pull tab or pin 3617 that is connected to a release layer3621 that may be removed (e.g., by pulling a pull tab 3613) to removethe ‘used’ hydrogel and expose a second ‘clean’ hydrogel beneath. Theelectrodes may make electrical connection by connecting through aflexible substrate onto which a conductive trace connecting to the firstand second electrodes are coupled to a clip or attachment 3641 on thecontrol circuit, as shown. Thus, the control circuity is connected via aflexile connection to the substrate and the control circuit is alsoflexibly connected via two or more wires, to the power source (e.g.,battery).

FIG. 36 shows another example of an apparatus in which the removal ofthe outer hydrogel by removing the release layer may also pull a secondtab that allows the second waveform to be applied once skin contact isconfirmed. This example also illustrates the circuit interrupt (pulltab) and is shown without the elastomeric cover material. FIGS. 37A and37B illustrate alternative variations of neuromodulator apparatuses.

In FIG. 37A, the battery 3708 is arranged at an angle to the controlcircuity 3713 and a circuit interrupt (pull tab 3711) is interposed in aclip 3715 on the control circuitry, preventing the battery from makingelectrical contact with the control circuitry until the circuitinterrupt is removed, e.g., by pulling the tap out. FIG. 37 shows anexample of a bottom (skin-facing) surface 3722 of an apparatus, whichmay include the hydrogel material forming the electrodes.

As mentioned above, the device may run for a preset time (e.g., 1-15minutes, e.g., about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,etc. min), then stop. The device may then be removed and laterre-applied. In some variations the original hydrogel may be‘reactivated’ for attachment by adding a few drops of water to thehydrogel (bottom of electrode) and reapplied. Alternatively the outerhydrogel layer may be removed. Once the apparatus detects skin contact,it may again applying a waveform, for a second preset time. The waveformmay be the same or different; if the hydrogel outer layer is removed,the second waveform may be different (e.g., lower intensity) than thefirst waveform. The apparatus generally include a battery that permitsit to run for a preset time (e.g., max of 15 min. use 2× or 3×).

In use, any of the apparatuses described herein, for any intendedpurpose (e.g., to evoke an energized state, to evoke a relaxed state, toenhance a cognitive function (e.g., memory, etc.), or to treat anindication, e.g., an inflammatory indication such as psoriasis, etc.)the method may generally include removing a circuit interrupt to allowthe circuitry to detect skin contact, and applying electricalstimulation in a predetermined waveform until the treatment is completeor the device is removed. FIG. 38A illustrates one example of this.

In FIG. 38A, the generic method may include activating, e.g., by pullinga tab (circuit interrupt) from the side of theneurostimluator/neuromodulator (“patch”). Once in a standby mode, theneuromodulator may be applied, e.g., to the neck (mastoid) 3401, or anyother appropriate region of the body. FIG. 38B illustrates one exampleof a method of applying the neurostimlator 3805 to the mastoid region,e.g., behind the ear. For example, the neurostimluator/neuromodulatormay be placed behind the ear on frim muscle and pressed firmly in place,while avoiding hair. 3403.

Once applied, the device may be activated to deliver the pre-definedwaveform. For example, the apparatus may be active for waveform deliverytime (e.g., 5 min, 7 min, 10 min, 12 min, 15 min, etc.). The device maybe removed if the subject feels any discomfort or strong itching. If thedevice is removed during application of waveform, it may restart a newstimulation period (e.g., 5 min) when reapplied 3405. Once the waveformis complete, the device may be removed, as it will enter into a stopmode, which may require a time delay and/or a second activation (e.g.,pull tab, etc.) before it may delver a second/subsequent dose 3507;optionally, the device may be re-used (in some variations, apply dropsof water to hydrogel and reapply; optionally remove outer hydrogel byremoving release layer) 3509.

In variations in which a second (or subsequent) dose may be applied, thesecond or subsequent dose may be different than the first dose. Forexample, in variations in which the initial or first hydrogel layer isremoved (e.g., by pulling off the outer hydrogel as shown in FIGS.39A-39C, the second or subsequent waveform may be adjusted so that thewaveforms delivered are approximately equivalent; thus, the intensity ofthe second waveform may be lower than the intensity of the first dose.

FIG. 39D illustrate an example of a neuromodulator 3906 and packaging(e.g., foil packet 3909). The apparatus may be sealed in the foil packetand removed by treating it open. To activate the device, a pull tab maybe removed and the device may be peeled form the backing and applieddirectly to the skin.

The apparatuses herein may include multiple layers of gel (e.g.,hydrogel) that may be removed to expose a clean hydrogel for repeateduse. For example, FIGS. 40-47 illustrate one exemplary method of forminga neuromodulator apparatus having multiple layers of hydrogel. FIG. 40is one example of a partial view of a neuromodulator including a pair ofconcentrically arranged electrode (electrode trace and conductive andadhesive hydrogel, each connected to a control circuitry). The first gellayer 4001 is shown as an electrolyte on silver electrode. Theconductive traces 4003 connect the electrodes to the control circuitry4509 and are flexible.

FIG. 41 is an example of a two-part release layer (configured as twoseparate release layers) for use with a neuromodulator apparatus asdescribed herein. In this example, an outer cover (e.g., an elastomericcover) is not yet included, and thus the control circuitry is exposed;the power source (e.g., battery) has also not yet been added. Therelease layer 4103 may be, for example, a hydrophobic film, such as awax paper or silicone film. Holes 4105 in the release layer may provideelectrical conductivity from the first hydrogel layer to the second gellayer.

In the example shown in FIGS. 40-47, the limited-number-of-useneuromodulator apparatus with a pair of release layers (in somevariations only a single release layer may be used, as shown in FIGS.34A and 34C, above). FIG. 42 shows placement of a first release layer onthe second (inner) electrode; FIGS. 43 and 44 show placement of theouter release layer on the first (outer) electrode that isconcentrically around the second electrode. The release layer mayinclude a release layer pull tab 4303. FIG. 45 illustrates placement ofa second gel layer 4505 for the second (inner) electrode. The first gellayer 4507 is visible through the holes in the release layer. FIG. 46shows placement of the second gel layer 4611 for the first (outer)electrode.

FIG. 47 illustrates the example the assembled limited-number-of-useneuromodulator apparatus assembled as shown in FIGS. 42-46. Thisvariation includes multiple (e.g., 2) layers of conductive gel; afterthe first use a layer of the gel may be removed, leaving the fresh underlayer. In this example, separate pull-tabs 4303, 4303′ may remove theinner and outer gel regions after use; these may be combined into asingle release layer.

FIGS. 48 and 49 illustrate examples of pendulum waveforms that may beused with a strong (FIG. 48) and mild (FIG. 49) stimulation waveforms.FIG. 48 shown one example of an energizing waveform that is configuredto result in an energizing effect. As sown in FIG. 48, the parametersfor the pendulum waveform are shown. At each defined (pre-defined) pointin time, the frequency, pulse width %, and intensity are indicated. Thiswaveform description may be encoded into firmware, software of hardwarefor running off of the control circuity. Similarly, FIG. 49 showsanother example of a stimulation/neuromodulation waveform.

FIG. 50 is another example of a limited-number-of use neuromodulator asdescribed herein. In FIG. 50 the device includes a battery that isstacked directly onto the backing and the other layers forming theapparatus. The dimensions and materials indicated are for illustrationonly; other dimensions and materials may be used.

FIG. 51 is an example prototype of a neuromodulator formed of a wovenmaterial (in this example a stainless steel yarn 5105) having electrodesformed one a woven substrate. A lead wire 5107 is woven into thesubstrate, and the lead wire exits 5109 to connect to the controlcircuitry 5111 (e.g., PCB). Similarly, FIG. 52A is an example of a testof a woven electrode similar to the variation shown in FIG. 51. Thewoven lead wire 5107 connects to a stimulation source, and to the wovenelectrode 5113. A test electrode 5115 is connected through the gel tothe neural stimulation electrode. FIG. 52B illustrates transmission of atest waveform using the prototype neuromodulator shown in FIG. 52A,showing a waveform 5117 picked up through coupling to the gel (shownhaving a full strength neural modulation electric current comping fromthe 3D woven electrode).

FIG. 53 is a prototype of an alternative design of a neuromodulatorsimilar to that shown in FIG. 51, having electrodes formed one a wovensubstrate. In FIG. 53, the apparatus includes stainless steel wire andthe electrode, woven into the nylon substrate. This design may be highlyefficient, since the stainless wire is of very low resistance. The oxidelayer on the stainless steel wire may provide a resistance in theZ-direction (direction out of the paper) to distribute the currentevenly. A miniature control circuitry 5305 is pre-programed with aneural modulation waveform(s). The contiguous lead wire may extend outof plane and connect to the control circuitry through the back side.

FIG. 54 is a prototype of an alternative design of a neuromodulatorsimilar to that shown in FIG. 51, having electrodes formed one a wovensubstrate. The density of the weave may be adjusted to provide moreconductivity where needed. In This example, a high density 5409 weaveportion may provide a central conductor to distribute electrical currentto lateral branches for X, Y plane distribution of electric current. Aconductor is connect to the control circuity 5411 out of the plane ofthe back side of the fabric.

FIG. 55 is another example of a prototype of an alternative design of aneuromodulator having electrodes formed one a woven substrate, similarto that shown in FIG. 51. The woven lead wire on the back side may beinsulated by the fabric so that the user is not exposed to a voltagefrom the lead wire. The control circuitry 5511 may be placed on the backside of the apparatus without any additional routing of the lead wire tothe back side. The woven lead wire 5507 may therefore be passed throughthe fabric 5515 serving as an insulator (electric insulator).

In general, the methods and apparatuses described herein may be usedwith or as part of one or more of: transdermal electric stimulation(“TES”), transcranial alternating current stimulation (“tACS”),transcranial direct current stimulation (“tDCS”), cranial electrotherapystimulation (“CES”), transcranial random noise stimulation (“tRNS”),trigeminal nerve stimulation (“TNS”), and vagal nerve stimulation(“VNS”), amongst other forms known to those skilled in the art.

Memory Enhancement

Any of the apparatuses described herein may be used for enhancingmemory.

For example, FIGS. 56A-56B show one example of a neuromodulator similarto those described above (e.g., in FIGS. 31A-31H and 32A-32H) that areconfigured to have a third electrode (e.g., cathode) and may be used forimproving a subject's cognitive state, and in particular, memory. Forexample, FIG. 56A shows a front view of a neuromodulator apparatus 5600(showing the fabric cover wrapping around and covering the battery andcontrol circuitry), while FIG. 56B shows the neuromodulator from theback view, showing the electrodes (including the hydrogel forming theelectrodes).

The device may be worn by a subject and used to improve memory. Theprototype apparatus shown in FIGS. 56A-56B includes three electrodes ina center-surround, source-sink pattern, configured as an anode 5605,first cathode 5607 and second cathode 5609. The device may be appliedover E27/E29 (on the temples) and over E12 (midline of the forehead) asshown in FIG. 50. In this example, the electrode at E27 is the anode(this is the center circle in the annular design of the apparatus),while the electrode on E29 is the outer electrode (cathode) formed bythe ring around the anode at E27. As shown in FIG. 57, this concentricelectrode is placed at the temple, creating the electric field on thelower middle portion of the brain, as shown in FIG. 59. The thirdelectrode, a cathode, is placed at the E12 position, shown in FIG. 27 asthe middle of the forehead. As shown in FIG. 59, the electrode at E12creates the field at the frontal lobe (left side of the brain) 5909 fromthe second cathode, and synchronized fields at the temporal region 5911from the first cathode. The waveform applied may include a theta-likewave (e.g., frequency of between 4-8 Hz) that may force these two brainregion to be synchronized thereby enhancing the memory function of thebrain. Two or more frequencies may be used for memory enhancements: thetheta-like waves (low frequency), and a higher frequency componentcorresponding to Gamma waves.

When a feature or element is herein referred to as being “on” anotherfeature or element, it can be directly on the other feature or elementor intervening features and/or elements may also be present. Incontrast, when a feature or element is referred to as being “directlyon” another feature or element, there are no intervening features orelements present. It will also be understood that, when a feature orelement is referred to as being “connected”, “attached” or “coupled” toanother feature or element, it can be directly connected, attached orcoupled to the other feature or element or intervening features orelements may be present. In contrast, when a feature or element isreferred to as being “directly connected”, “directly attached” or“directly coupled” to another feature or element, there are nointervening features or elements present. Although described or shownwith respect to one embodiment, the features and elements so describedor shown can apply to other embodiments. It will also be appreciated bythose of skill in the art that references to a structure or feature thatis disposed “adjacent” another feature may have portions that overlap orunderlie the adjacent feature.

Terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention.For example, as used herein, the singular forms “a”, “an” and “the” areintended to include the plural forms as well, unless the context clearlyindicates otherwise. It will be further understood that the terms“comprises” and/or “comprising,” when used in this specification,specify the presence of stated features, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, steps, operations, elements, components, and/orgroups thereof. As used herein, the term “and/or” includes any and allcombinations of one or more of the associated listed items and may beabbreviated as “/”.

Spatially relative terms, such as “under”, “below”, “lower”, “over”,“upper” and the like, may be used herein for ease of description todescribe one element or feature's relationship to another element(s) orfeature(s) as illustrated in the figures. It will be understood that thespatially relative terms are intended to encompass differentorientations of the device in use or operation in addition to theorientation depicted in the figures. For example, if a device in thefigures is inverted, elements described as “under” or “beneath” otherelements or features would then be oriented “over” the other elements orfeatures. Thus, the exemplary term “under” can encompass both anorientation of over and under. The device may be otherwise oriented(rotated 90 degrees or at other orientations) and the spatially relativedescriptors used herein interpreted accordingly. Similarly, the terms“upwardly”, “downwardly”, “vertical”, “horizontal” and the like are usedherein for the purpose of explanation only unless specifically indicatedotherwise.

Although the terms “first” and “second” may be used herein to describevarious features/elements (including steps), these features/elementsshould not be limited by these terms, unless the context indicatesotherwise. These terms may be used to distinguish one feature/elementfrom another feature/element. Thus, a first feature/element discussedbelow could be termed a second feature/element, and similarly, a secondfeature/element discussed below could be termed a first feature/elementwithout departing from the teachings of the present invention.

Throughout this specification and the claims which follow, unless thecontext requires otherwise, the word “comprise”, and variations such as“comprises” and “comprising” means various components can be co-jointlyemployed in the methods and articles (e.g., compositions and apparatusesincluding device and methods). For example, the term “comprising” willbe understood to imply the inclusion of any stated elements or steps butnot the exclusion of any other elements or steps.

In general, any of the apparatuses and methods described herein shouldbe understood to be inclusive, but all or a sub-set of the componentsand/or steps may alternatively be exclusive, and may be expressed as“consisting of” or alternatively “consisting essentially of” the variouscomponents, steps, sub-components or sub-steps.

As used herein in the specification and claims, including as used in theexamples and unless otherwise expressly specified, all numbers may beread as if prefaced by the word “about” or “approximately,” even if theterm does not expressly appear. The phrase “about” or “approximately”may be used when describing magnitude and/or position to indicate thatthe value and/or position described is within a reasonable expectedrange of values and/or positions. For example, a numeric value may havea value that is +/−0.1% of the stated value (or range of values), +/−1%of the stated value (or range of values), +/−2% of the stated value (orrange of values), +/−5% of the stated value (or range of values), +/−10%of the stated value (or range of values), etc. Any numerical valuesgiven herein should also be understood to include about or approximatelythat value, unless the context indicates otherwise. For example, if thevalue “10” is disclosed, then “about 10” is also disclosed. Anynumerical range recited herein is intended to include all sub-rangessubsumed therein. It is also understood that when a value is disclosedthat “less than or equal to” the value, “greater than or equal to thevalue” and possible ranges between values are also disclosed, asappropriately understood by the skilled artisan. For example, if thevalue “X” is disclosed the “less than or equal to X” as well as “greaterthan or equal to X” (e.g., where X is a numerical value) is alsodisclosed. It is also understood that the throughout the application,data is provided in a number of different formats, and that this data,represents endpoints and starting points, and ranges for any combinationof the data points. For example, if a particular data point “10” and aparticular data point “15” are disclosed, it is understood that greaterthan, greater than or equal to, less than, less than or equal to, andequal to 10 and 15 are considered disclosed as well as between 10 and15. It is also understood that each unit between two particular unitsare also disclosed. For example, if 10 and 15 are disclosed, then 11,12, 13, and 14 are also disclosed.

Although various illustrative embodiments are described above, any of anumber of changes may be made to various embodiments without departingfrom the scope of the invention as described by the claims. For example,the order in which various described method steps are performed mayoften be changed in alternative embodiments, and in other alternativeembodiments one or more method steps may be skipped altogether. Optionalfeatures of various device and system embodiments may be included insome embodiments and not in others. Therefore, the foregoing descriptionis provided primarily for exemplary purposes and should not beinterpreted to limit the scope of the invention as it is set forth inthe claims.

The examples and illustrations included herein show, by way ofillustration and not of limitation, specific embodiments in which thesubject matter may be practiced. As mentioned, other embodiments may beutilized and derived there from, such that structural and logicalsubstitutions and changes may be made without departing from the scopeof this disclosure. Such embodiments of the inventive subject matter maybe referred to herein individually or collectively by the term“invention” merely for convenience and without intending to voluntarilylimit the scope of this application to any single invention or inventiveconcept, if more than one is, in fact, disclosed. Thus, althoughspecific embodiments have been illustrated and described herein, anyarrangement calculated to achieve the same purpose may be substitutedfor the specific embodiments shown. This disclosure is intended to coverany and all adaptations or variations of various embodiments.Combinations of the above embodiments, and other embodiments notspecifically described herein, will be apparent to those of skill in theart upon reviewing the above description.

What is claimed is:
 1. A wearable neuromodulator device, the devicecomprising: a flexible substrate; a first electrode; a second electrodeon the flexible substrate; a battery; a control circuitry coupled to thefirst electrode and the second electrode, wherein the control circuitryis configured to deliver a predefined waveform between the first andsecond electrodes when the battery is powering the control circuitry;and an elastic cover wherein the battery and control circuitry arebetween the cover and the flexible substrate, further wherein the deviceweighs 20 g or less, has a maximum thickness of 7 mm or less, and amaximum diameter of 10 cm or less.
 2. The device of claim 1, wherein theelastic cover comprises an elastomeric fabric.
 3. The device of claim 1,wherein the elastic cover comprises an elastomeric cotton.
 4. The deviceof claim 1, wherein the elastic cover comprise a nonwoven elastomericmaterial.
 5. The device of claim 1, wherein the battery and controlcircuitry are at least partially wrapped in the elastic cover.
 6. Thedevice of claim 1, wherein the elastic cover is secured over theflexible substrate.
 7. The device of claim 1, wherein the elastic coveris adhesively secured to the flexible substrate.
 8. The device of claim1, further comprising a frame securing the battery and the controlcircuitry, wherein the frame is covered by the elastic cover.
 9. Thedevice of claim 1, wherein the first electrode further comprises a firsthydrogel and the second electrode further comprises a second hydrogel.10. The device of claim 1, wherein the waveform has a frequency ofbetween 100 Hz and 15 KHz and delivers a charge per phase of between0.1-10 microCoulombs.
 11. The device of claim 1, wherein the predefinedwaveform is configured to run for 15 minutes or less.
 12. A wearableneuromodulator device, the device comprising: a flexible substrate; afirst electrode on the flexible substrate; a second electrode on theflexible substrate; a battery; a control circuitry coupled to the firstelectrode and the second electrode, wherein the control circuitry isconfigured to deliver a predefined waveform between the first and secondelectrodes when the battery is powering the control circuitry; and anelastic cover comprising an elastomeric fabric that is adhesivelysecured to the flexible substrate wherein the battery and controlcircuitry are at least partially wrapped in the cover.
 13. The device ofclaim 12, further wherein the device weighs 20 g or less, has a maximumthickness of 7 mm or less, and a maximum diameter of 10 cm or less. 14.The device of claim 12, wherein the elastic cover comprises anelastomeric cotton.
 15. The device of claim 12, wherein the elasticcover comprise a nonwoven elastomeric material.
 16. The device of claim12, further comprising a frame securing the battery and the controlcircuitry, wherein the frame is covered by the elastic cover.
 17. Thedevice of claim 12, wherein the first electrode further comprises afirst hydrogel and the second electrode further comprises a secondhydrogel.
 18. The device of claim 12, wherein the waveform has afrequency of between 100 Hz and 15 KHz and delivers a charge per phaseof between 0.1-10 microCoulombs.
 19. The device of claim 12, wherein thepredefined waveform is configured to run for 15 minutes or less.
 20. Awearable neuromodulator device, the device comprising: a flexiblesubstrate; a first electrode that is concentrically arranged around asecond electrode, wherein the first and second electrodes are on theflexible substrate; a battery; a control circuitry coupled to the firstelectrode and the second electrode, wherein the control circuitry isconfigured to deliver a predefined waveform between the first and secondelectrodes when the battery is powering the control circuitry; and anelastomeric fabric cover attached to the flexible substrate, wherein thebattery and control circuitry are between the cover and the flexiblesubstrate, further wherein the device weighs 20 g or less.